Absorbed dose profiles for 32P, 90Y, 188Re, 177Lu, 153Sm and 169Er: radionuclides used in radiosynoviortheses treatment | Revista Española de Medicina Nuclear e Imagen Molecular

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Margen superior izquierdo: cámara emisora y detectora de infrarrojos. Margen inferior derecho: pantalla de monitorización del ciclo respiratorio. En la imagen central se puede ver el posicionado del paciente momentos antes de la adquisición de la exploración." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.M. García Vicente, A. Soriano Castrejón, P. Talavera Rubio, V.M. Poblete García, A. Palomar Muñoz, I. Cepedello Boiso, B. González García, J.M. Cordero García, M. Bellón Guardia, J.P. Pilkington Woll" "autores" => array:10 [ 0 => array:2 [ "Iniciales" => "A.M." "apellidos" => "García Vicente" ] 1 => array:2 [ "Iniciales" => "A." "apellidos" => "Soriano Castrejón" ] 2 => array:2 [ "Iniciales" => "P." "apellidos" => "Talavera Rubio" ] 3 => array:2 [ "Iniciales" => "V.M." "apellidos" => "Poblete García" ] 4 => array:2 [ "Iniciales" => "A." "apellidos" => "Palomar Muñoz" ] 5 => array:2 [ "Iniciales" => "I." 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Albuerne, M.A. Montano Delgado" "autores" => array:4 [ 0 => array:3 [ "Iniciales" => "M." "apellidos" => "Torres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "E." "apellidos" => "Ayra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "O." "apellidos" => "Albuerne" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "M.A." "apellidos" => "Montano Delgado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Radiation Protection Department, Isotopes Centre, Carretera la Rada, Km 3 1/2 Havana, Cuba" "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Hospital General Docente Enrique Cabrera, Havana, Cuba" "etiqueta" => "b" "identificador" => "affb" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Autor para correspondencia." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Perfiles de dosis absorbida para 32P, 90Y, 188Re, 177Lu, 153Sm y 169Er : radionuclidos usados en el tratamiento de radiosinoviortesis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v28n04-13140119fig1.jpg" "Alto" => 1284 "Ancho" => 1632 "Tamanyo" => 222438 ] ] "descripcion" => array:1 [ "en" => "Absorbed doses profiles (Gy*cm 2/h*MBq) as a function of distance into the diseased synovium." ] ] ] "textoCompleto" => "IntroductionThe treatment of inflammatory arthropathies is aimed to diminish the inflammation, relieve the pain, improve the functional capability and induce the remission of the disease. Although every case requires specific therapeutic guidelines<a href="#bib1" class="elsevierStyleCrossRefs">1</a>, some joints may not experience clinical improvement, so other complementary therapies should be used. Most commons are intrarticular corticoids, chemical synovectomy, surgical synovectomy and radiosynoviortheses (RSV). An alternative to surgery is RSV, which eliminates the inflamed tissue by means of beta radiation. The first published reports of this last treatment are as back as to 1924<a href="#bib2" class="elsevierStyleCrossRefs">2</a>. In the clinical practice, the first results were published in 1952<a href="#bib3" class="elsevierStyleCrossRefs">3</a> and were followed in the 60s with the inclusion of Y-90<a href="#bib4" class="elsevierStyleCrossRefs">4</a>,<a href="#bib5" class="elsevierStyleCrossRefs">5</a>.The RSV is the injection of a radioactive substance inside any synovial cavity, in such way that the injected radionuclide makes contact with the synovial membrane. This substance is rapidly phagocytized by the synovial lining cells. During the radioactive decay of the injected radionuclide, a therapeutic dose will be delivered to the synovial tissue destroying it. The energy of the beta emitters used in radiosynoviortheses range from 0.34MeV (0.33mm penetration in tissue) in the case of Er-169 to 2.27MeV (3.6mm penetration in tissue) for the Y-90. The half life of these isotopes goes from 2.3 hrs (Dy-165) to 27.8 days (Cr-51)<a href="#bib6" class="elsevierStyleCrossRefs">6</a>. Nowadays, the selection of the radionuclide to be used depends on the size of the joint to be treated. Thus, the smaller the joint, the lower should be the energy and therefore the penetration. These facts led to the use of fixed radionuclides for specific joints. The first works on the assessment of doses to the patients in RSV were published in the 80s and early 90s<a href="#bib7" class="elsevierStyleCrossRefs">7</a>,<a href="#bib8" class="elsevierStyleCrossRefs">8</a>,<a href="#bib9" class="elsevierStyleCrossRefs">9</a>,<a href="#bib10" class="elsevierStyleCrossRefs">10</a>. As new radiopharmaceuticals offering many potential advantages for RSV are being developed in our centre, it seems prudent to evaluate the dose distribution of some radionuclides that have been used or tested in animal and human models: 32P, 90Y, 188Re, 186Re 177Lu, 153Sm and 169Er.The method used to assess the dosimetry in RSV is known as the Monte Carlo method. Nevertheless, while it provides an improved technique for calculating local dosimetry, there are still clear difficulties involved in relating this dosimetry to clinical outcome. Although the goal of radiation synovectomy procedure is ablation of the inflamed synovial tissue, very few studies have been performed to determine the dose required to reach this goal. The rationale for choosing a particular administered dose of a given isotope for a given joint is obscure. As with other form of therapy, clinical success in RSV will depend on the thickness of the synovium to be treated and the proximity of the non target organs to the joint (bone and articular cartilage), so it will be based in the absorbed dose and the penetration of the radiation emitted by the radionuclide.The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The radionuclides involved were those previously mentioned. The therapeutic range of each radionuclides in synovial tissue were also calculated. The therapeutic range is defined as the deepness at which the absorbed dose equals the 10% of the maximum dose deposited in the synovial surface. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated.Materials and methodsThe synovial joint is basically the articular cartilage, bone and tissue (synovial membrane). In <a href="#tbl1" class="elsevierStyleCrossRefs">tabla 1</a> is shown the composition and density of every constituent according to Johnson and Yanch<a href="#bib8" class="elsevierStyleCrossRefs">8</a>.Table 1. Composition and density of components of the synovial joint<a name="tbl1" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>Elements</td><td>H</td><td>C</td><td>N</td><td>O</td><td>Na</td><td>Mg</td><td>P</td><td>S</td><td>Ca</td><td>Cl</td><td>ρ (g/cm3)</td></tr><tr align="left"><td>Bone (%)</td><td>3.4</td><td>15.5</td><td>4.2</td><td>43.5</td><td>0.1</td><td>0.2</td><td>10.3</td><td>0.3</td><td>22.5</td><td>–</td><td>1.92</td></tr><tr align="left"><td>Articular cartilage (%)</td><td>9.6</td><td>9.9</td><td>2.2</td><td>74.4</td><td>0.5</td><td>–</td><td>2.2</td><td>0.9</td><td>–</td><td>0.3</td><td>1.1</td></tr><tr align="left"><td>Tissue (%)</td><td>10.0</td><td>14.9</td><td>3.5</td><td>71.6</td><td>–</td><td>–</td><td>–</td><td>–</td><td>–</td><td>–</td><td>1.0</td></tr></table>The energy of beta particles used in RSV should be enough as to deliver a dose of radiation good for destroying the synovial tissue and yet not as high as to expose unnecessarily the cartilage and bone. In <a href="#tbl2" class="elsevierStyleCrossRefs">tabla 2</a> are listed the energetic characteristics of the radionuclides assessed in this work.Table 2. Energetic characteristic of the assessed radionuclides<a name="tbl2" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>Radionuclides</td><td>Y-90</td><td>P-32</td><td>Re-188</td><td>Lu-177</td><td>Sm-153</td><td>Er-169</td></tr><tr align="left"><td>T1/2</td><td>64.1h</td><td>14.3 days</td><td>16.98h</td><td>6.71 days</td><td>46.7h</td><td>9.4 days</td></tr><tr align="left"><td>Emission type</td><td>Beta</td><td>Beta</td><td>Beta, gamma, electron</td><td>Beta, gamma, electron</td><td>Beta, gamma, electron</td><td>Beta, gamma, electron</td></tr></table>The MCNP4C Monte Carlo code was used to perform the dosimetry calculations. MCNP is a general-purpose Monte Carlo N-Particle code that can be used for neutron, photon, electron, or coupled neutron/photon/electron transport. MCNP4C is the first major release of MCNP since version 4B<a href="#bib11" class="elsevierStyleCrossRefs">11</a>. The beta spectrum of the radionuclides listed in <a href="#tbl2" class="elsevierStyleCrossRefs">tabla 2</a> was downloaded from www.doseinfo-radar <a href="#bib12" class="elsevierStyleCrossRefs">12</a> and the characteristics of the gamma and/or electronic emission are the ones in the software Radiation Decay<a href="#bib13" class="elsevierStyleCrossRefs">13</a>.To determine the therapeutic range (X90), an isotropic point source was simulated in the centre of various concentric spheres of different radii. These radii ranged from 1mm to 10mm (increasing 1mm at a time) for all radionuclides but for Er-169. In this case, the radii ranged from 0.1mm to 1mm (0.1mm at a time).The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The synovium area can be estimated through computer tomography (CT)<a href="#bib7" class="elsevierStyleCrossRefs">7</a>. The height of the cylinder represents different stages of the progression of the rheumatoid arthritis (RA)<a href="#bib8" class="elsevierStyleCrossRefs">8</a>. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius). The S value as a function of distance into the diseased synovium and articular cartilage for each of the 6 beta emitting radionuclides mentioned earlier were simulated incorporating very thin cylindrical slabs of tissue and articular cartilage to the original model. S = E m * 576.7 * 1 0 - 3 The S (Gy/h*MBq) values have been calculated for different pair of source-target organs and for some radionuclides of interest in Nuclear Medicine<a href="#bib14" class="elsevierStyleCrossRefs">14</a>. In this paper, using Monte Carlo computer calculations, the S values for each proposed model were obtained calculating the mean absorbed energy (E) per disintegration deposited in a target mass (synovial membrane and articular cartilage), divided by the tissue mass (m) and multiplied by 576.7E-03 to obtain the absorbed dose level per cumulated activity in the source region, Gy/h*MBq. The basic equation for this situation is:where m: tissue mass (g), E: mean absorbed energy (E) per disintegration deposited in a target mass (MeV). D t = S × 1.44 × T 1 / 2 f ı ´ sico × A o If we consider that the radionuclide decays completely in the joint, so no leakage effect is taken into account, important aspect to keep in mind, the dose absorbed in the synovial membrane is obtained through the Eq. <a href="#eq2" class="elsevierStyleCrossRefs"></a>.where S: S-value (Gy/h*MBq), T1/2: half life, A0: injected activity into the articular cavity.For all cases, a sufficient number of electron and photon transport histories were generated to produce statistically reliable energy tallies, with relative errors less than 0.10. Also, the Bremsstrahlung radiation was considered in the calculations.Analysis and discussion of resultsSynovial membraneS-values for synovial membranes with different synovium size are shown in <a href="#tbl3" class="elsevierStyleCrossRefs">tabla 3</a>. As the area of the inflamed synovium increases, diminishes the value of the absorbed dose rate in the synovial membrane. Studies with 90Y usually apply an average administered activity of 185MBq for arthritic knee patients with synovium area of 250cm2. This value of administered activity will deliver approximately 130Gy in the synovial membrane according to our model (S-value=0.007). If we wish to obtain the same therapeutic effect in the synovial membrane of an arthritic wrist with 50cm2 of synovium area (S-value=0.035), it only will be necessary to inject 37MBq of 90Y. In this case it is considered that the radionuclide decays completely in the joint (Eq. <a href="#eq2" class="elsevierStyleCrossRefs"></a>).Table 3. S-Values (Gy/MBq*h) for different synovium sizes and thickness of synovial lining cells.<a name="tbl3" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>A(cm2)</td><td rowspan="0" colspan="12">Thickness of synovial lining cells</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td></td><td rowspan="0" colspan="6">0.01cm</td><td rowspan="0" colspan="6">0.015cm</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td></td><td>90Y</td><td>32P</td><td>188Re</td><td>177Lu</td><td>153Sm</td><td>169Er</td><td>90Y</td><td>32P</td><td>188Re</td><td>177Lu</td><td>153Sm</td><td>169Er</td></tr><tr align="left"><td>13</td><td>0.152</td><td>0.154</td><td>0.325</td><td>0.335</td><td>0.294</td><td>0.295</td><td>0.144</td><td>0.146</td><td>0.291</td><td>0.277</td><td>0.243</td><td>0.240</td></tr><tr align="left"><td>20</td><td>0.098</td><td>0.099</td><td>0.208</td><td>0.214</td><td>0.188</td><td>0.189</td><td>0.092</td><td>0.094</td><td>0.186</td><td>0.177</td><td>0.156</td><td>0.154</td></tr><tr align="left"><td>28</td><td>0.068</td><td>0.069</td><td>0.145</td><td>0.149</td><td>0.131</td><td>0.131</td><td>0.064</td><td>0.065</td><td>0.130</td><td>0.123</td><td>0.108</td><td>0.107</td></tr><tr align="left"><td>38</td><td>0.050</td><td>0.051</td><td>0.106</td><td>0.109</td><td>0.096</td><td>0.096</td><td>0.047</td><td>0.048</td><td>0.095</td><td>0.091</td><td>0.080</td><td>0.078</td></tr><tr align="left"><td>50</td><td>0.038</td><td>0.039</td><td>0.081</td><td>0.084</td><td>0.074</td><td>0.074</td><td>0.036</td><td>0.037</td><td>0.073</td><td>0.069</td><td>0.061</td><td>0.060</td></tr><tr align="left"><td>64</td><td>0.030</td><td>0.031</td><td>0.064</td><td>0.066</td><td>0.058</td><td>0.058</td><td>0.029</td><td>0.029</td><td>0.058</td><td>0.055</td><td>0.048</td><td>0.047</td></tr><tr align="left"><td>79</td><td>0.024</td><td>0.025</td><td>0.052</td><td>0.054</td><td>0.047</td><td>0.047</td><td>0.023</td><td>0.024</td><td>0.047</td><td>0.044</td><td>0.039</td><td>0.038</td></tr><tr align="left"><td>95</td><td>0.020</td><td>0.020</td><td>0.043</td><td>0.044</td><td>0.039</td><td>0.039</td><td>0.019</td><td>0.019</td><td>0.039</td><td>0.037</td><td>0.032</td><td>0.032</td></tr><tr align="left"><td>113</td><td>0.017</td><td>0.017</td><td>0.036</td><td>0.037</td><td>0.033</td><td>0.033</td><td>0.016</td><td>0.016</td><td>0.032</td><td>0.031</td><td>0.027</td><td>0.027</td></tr><tr align="left"><td>133</td><td>0.014</td><td>0.015</td><td>0.031</td><td>0.032</td><td>0.028</td><td>0.028</td><td>0.014</td><td>0.014</td><td>0.028</td><td>0.026</td><td>0.023</td><td>0.023</td></tr><tr align="left"><td>154</td><td>0.013</td><td>0.013</td><td>0.027</td><td>0.027</td><td>0.024</td><td>0.024</td><td>0.012</td><td>0.012</td><td>0.024</td><td>0.023</td><td>0.020</td><td>0.020</td></tr><tr align="left"><td>177</td><td>0.011</td><td>0.011</td><td>0.023</td><td>0.024</td><td>0.021</td><td>0.021</td><td>0.010</td><td>0.010</td><td>0.021</td><td>0.020</td><td>0.017</td><td>0.017</td></tr><tr align="left"><td>201</td><td>0.010</td><td>0.010</td><td>0.020</td><td>0.021</td><td>0.018</td><td>0.018</td><td>0.009</td><td>0.009</td><td>0.018</td><td>0.017</td><td>0.015</td><td>0.015</td></tr><tr align="left"><td>227</td><td>0.008</td><td>0.009</td><td>0.018</td><td>0.019</td><td>0.016</td><td>0.016</td><td>0.008</td><td>0.008</td><td>0.016</td><td>0.015</td><td>0.013</td><td>0.013</td></tr><tr align="left"><td>254</td><td>0.008</td><td>0.008</td><td>0.016</td><td>0.017</td><td>0.015</td><td>0.015</td><td>0.007</td><td>0.007</td><td>0.014</td><td>0.014</td><td>0.012</td><td>0.012</td></tr><tr align="left"><td></td></tr><tr align="left"><td></td><td>0.02cm</td><td>0.025cm</td></tr><tr align="left"><td>A(cm2)</td><td>90Y</td><td>32P</td><td>188Re</td><td>177Lu</td><td>153Sm</td><td>169Er</td><td>90Y</td><td>32P</td><td>188Re</td><td>177Lu</td><td>153Sm</td><td>169Er</td></tr><tr align="left"><td>13</td><td>0.138</td><td>0.140</td><td>0.264</td><td>0.237</td><td>0.211</td><td>0.197</td><td>0.134</td><td>0.136</td><td>0.244</td><td>0.207</td><td>0.189</td><td>0.166</td></tr><tr align="left"><td>20</td><td>0.089</td><td>0.090</td><td>0.170</td><td>0.151</td><td>0.135</td><td>0.126</td><td>0.086</td><td>0.087</td><td>0.156</td><td>0.132</td><td>0.121</td><td>0.106</td></tr><tr align="left"><td>28</td><td>0.062</td><td>0.063</td><td>0.118</td><td>0.105</td><td>0.094</td><td>0.088</td><td>0.060</td><td>0.061</td><td>0.109</td><td>0.092</td><td>0.084</td><td>0.074</td></tr><tr align="left"><td>38</td><td>0.045</td><td>0.046</td><td>0.087</td><td>0.077</td><td>0.069</td><td>0.064</td><td>0.044</td><td>0.045</td><td>0.080</td><td>0.068</td><td>0.062</td><td>0.054</td></tr><tr align="left"><td>50</td><td>0.035</td><td>0.035</td><td>0.066</td><td>0.059</td><td>0.053</td><td>0.049</td><td>0.034</td><td>0.034</td><td>0.061</td><td>0.052</td><td>0.047</td><td>0.042</td></tr><tr align="left"><td>64</td><td>0.028</td><td>0.028</td><td>0.056</td><td>0.047</td><td>0.042</td><td>0.039</td><td>0.027</td><td>0.027</td><td>0.048</td><td>0.041</td><td>0.037</td><td>0.033</td></tr><tr align="left"><td>79</td><td>0.022</td><td>0.023</td><td>0.043</td><td>0.038</td><td>0.034</td><td>0.032</td><td>0.022</td><td>0.022</td><td>0.039</td><td>0.033</td><td>0.030</td><td>0.027</td></tr><tr align="left"><td>95</td><td>0.018</td><td>0.019</td><td>0.035</td><td>0.031</td><td>0.028</td><td>0.026</td><td>0.018</td><td>0.018</td><td>0.032</td><td>0.027</td><td>0.025</td><td>0.022</td></tr><tr align="left"><td>113</td><td>0.016</td><td>0.016</td><td>0.030</td><td>0.026</td><td>0.024</td><td>0.022</td><td>0.015</td><td>0.015</td><td>0.027</td><td>0.023</td><td>0.021</td><td>0.018</td></tr><tr align="left"><td>133</td><td>0.013</td><td>0.013</td><td>0.025</td><td>0.022</td><td>0.020</td><td>0.019</td><td>0.013</td><td>0.013</td><td>0.023</td><td>0.020</td><td>0.018</td><td>0.016</td></tr><tr align="left"><td>154</td><td>0.011</td><td>0.012</td><td>0.022</td><td>0.019</td><td>0.017</td><td>0.016</td><td>0.011</td><td>0.011</td><td>0.020</td><td>0.017</td><td>0.015</td><td>0.014</td></tr><tr align="left"><td>177</td><td>0.010</td><td>0.010</td><td>0.019</td><td>0.017</td><td>0.015</td><td>0.014</td><td>0.010</td><td>0.010</td><td>0.017</td><td>0.015</td><td>0.013</td><td>0.012</td></tr><tr align="left"><td>201</td><td>0.009</td><td>0.009</td><td>0.017</td><td>0.015</td><td>0.013</td><td>0.012</td><td>0.008</td><td>0.009</td><td>0.015</td><td>0.013</td><td>0.012</td><td>0.010</td></tr><tr align="left"><td>227</td><td>0.008</td><td>0.008</td><td>0.015</td><td>0.013</td><td>0.012</td><td>0.011</td><td>0.007</td><td>0.008</td><td>0.014</td><td>0.011</td><td>0.010</td><td>0.009</td></tr><tr align="left"><td>254</td><td>0.007</td><td>0.007</td><td>0.013</td><td>0.012</td><td>0.010</td><td>0.010</td><td>0.007</td><td>0.007</td><td>0.012</td><td>0.010</td><td>0.009</td><td>0.008</td></tr></table>Since electron emission energies and spectral shapes differ between β-active radionuclides, the absorbed dose penetration range can vary substantially from one radionuclide to another. Essentially, this effective penetration ranges determine the thickness of inflamed synovium that can be treated successfully. One way of evaluating this range is to establish the distance at which the absorbed dose equals the 10% of the dose deposited in the synovial membrane (X90). The X90 values for each of the six beta-emitting radionuclides considered in this paper are included in <a href="#tbl4" class="elsevierStyleCrossRefs">tabla 4</a>.Table 4. Therapeutic range (X90) for 90Y, 32P, 188Re, 177Lu, 153Sm, and 169Er<a name="tbl4" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td rowspan="0" colspan="6">X90 (mm)</td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td>90Y</td><td>32P2</td><td>188Re</td><td>177Lu</td><td>153Sm</td><td>169Er</td></tr><tr align="left"><td>2.22</td><td>2.1</td><td>2.1</td><td>1.3</td><td>1.6</td><td>0.18</td></tr></table>Note that X90 can be divided in three groups. The first group formed by 90Y, 32P and 188Re with X90=2mm, the second group (177Lu and 153Sm) with 1&#60;X90&#60;=2mm and the third one (169Er); X90&#60;1. These variations can be used to help the clinician performing RSV in selecting the best radionuclide for individual joint and synovium condition. No single radionuclide is ideally suited for use in every radiation synovectomy, since the thickness of inflamed synovium will differ from joint to joint and from patient to patient. In a large joint with thick synovial membrane, for example, deep penetration of the beta particles is desirable in order to sufficiently treat the inflamed tissue. In small joints with thin synovial membrane, this penetration represents an unnecessary radiation hazard to other normal structures around the joint.For example, for an arthritic knee, with thick synovium, the suited radionuclides to deliver a therapeutic dose in the synovial depth are 90Y, 32P and 188Re. An average administered activity of 185MBq of 90Y delivers a radiation absorbed dose of approximately 100Gy to 100 g-synovium. Since this dose of 90Y was shown to be efficacious in the treatment<a href="#bib15" class="elsevierStyleCrossRefs">15</a>, other investigators have used a “calculated 90Y dose equivalent” when administering other radionuclide.The <a href="#tbl5" class="elsevierStyleCrossRefs">tabla 5</a> shows activity values of 188Re and 32P to obtain the “90Y dose equivalent” in the synovial membrane (0.2mm thickness of synovial lining cells and 250cm2 of synovium area).Table 5. Values of activity administered of 188Re and 32P to obtain the “90Y dose equivalent” into the synovial membrane<a name="tbl5" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>Radionuclide</td><td>X90</td><td>S-value Gy/h*MBq</td><td>Absorbed dose (Gy)</td><td>Administered activity (MBq)</td></tr><tr align="left"><td>Y-90</td><td>2.22</td><td>0.007</td><td>130</td><td>185</td></tr><tr align="left"><td>P-32</td><td>2.1</td><td>0.007</td><td>130</td><td>37</td></tr><tr align="left"><td>Re-188</td><td>2.1</td><td>0.013</td><td>130</td><td>407</td></tr></table>Note the great differences in the activity administered, but not in the effective penetration ranges in tissue. In this case the radionuclide selection to treat the damaged tissue will depend on its availability. 32P and 90Y are the two isotopes most widely used today as the basis for RSV agents; however, these isotopes do not emit imageable gamma rays and thus are very difficult to obtain quantitative dosimetric information on patients treated with agents based on 32P and 90Y. These radionuclides are available in our centre. 188Re has the advantage of a tissue penetration equivalent to that of 90Y but a shorter half-life, important for leakage reduction<a href="#bib16" class="elsevierStyleCrossRefs">16</a>. It has a 155keV gamma ray, which would permit analysis of leakage to other organs by gamma camera imaging. The possibility of producing the isotope with an 188W-188Re generator would greatly extend its availability.Following the same procedure previously described with 90Y, 32P and 188Re in median and small joints with thin synovium depth, the most appropriate radionuclides are those with less X90. The <a href="#tbl6" class="elsevierStyleCrossRefs">tabla 6</a> shows the activity values of 177Lu and 153Sm to obtain the “90Y dose equivalent” in the synovial membrane of an arthritic wrist.Table 6. Values of activity administered of 177Lu and 153 Sm to obtain the “90Y dose equivalent” into the synovial membrane of an arthritics wrist (0.1mm thickness of the synovial membrane and 50cm2 of synovium area)<a name="tbl6" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>Radionuclide</td><td>X90</td><td>S-value Gy/h*MBq</td><td>Absorbed dose (Gy)</td><td>Administered activity (MBq)</td></tr><tr align="left"><td>177Lu</td><td>1.3</td><td>0.084</td><td>130</td><td>6.7</td></tr><tr align="left"><td>153Sm</td><td>1.6</td><td>0.074</td><td>130</td><td>26.1</td></tr></table>Both 177Lu and 153Sm, by their energetic properties, can be used to treat small joints in advanced stages of arthritis. On the other hand 169Er is used to treat small joints only<a href="#bib17" class="elsevierStyleCrossRefs">17</a>.The amount of radioactivity for a single intra-articular injection with 169Er depends on the joint size<a href="#bib18" class="elsevierStyleCrossRefs">18</a>:<ul><li>10–20 MBq for proximal or distal interphalangeal joints,</li><li>20–40 MBq for metacarpophalangeal or metatarsophalangeal joints,</li><li>20–80 MBq for trapeziometacarpal joints.</li></ul>Multiple joints may be treated simultaneously with a cumulative dose not exceeding 555MBq per patientThe absorbed dose estimated for a 169Er injected activity of 10 to 20MBq at a synovial depth of 0.1mm is 910 to 1820Gy<a href="#bib18" class="elsevierStyleCrossRefs">18</a>. This aspect should be taken into account to prescribe the activity in case of other radionuclides.In <a href="#tbl7" class="elsevierStyleCrossRefs">tabla 7</a> are shown the activity values of 177Lu and 153Sm to obtain the “169Er dose equivalent” in the synovial membrane of small joints (0.1mm thickness of synovial lining cells and 13cm2 of synovium area).Table 7. Values of activity administered of 177Lu and 153Sm to obtain the “169Er dose equivalent” in the synovial membrane of an arthritics small joint (0.1mm thickness of synovial lining cells and 10cm2 of synovium area)<a name="tbl7" class="elsevierStyleCrossRefs"></a><table><tr align="left"><td>Radionuclide</td><td>X90</td><td>S-value Gy/h*MBq</td><td>Absorbed dose (Gy)</td><td>Administered activity (MBq)</td></tr><tr align="left"><td>169Er</td><td>0.2</td><td>0.295</td><td>958</td><td>10</td></tr><tr align="left"><td>177Lu</td><td>1.3</td><td>0.335</td><td>958</td><td>12.3</td></tr><tr align="left"><td>153Sm</td><td>1.6</td><td>0.294</td><td>958</td><td>48.4</td></tr></table>This empirical approach to calculating the dose of a new radionuclide to be administered appears to provide basis to start new researches with different radionuclides. However, the nonexistence of theoretical sustentations for these calculations still make the clinical trials the only way to determine the dose of a new radionuclide that will be effective in a treatment. Thus, the clinical trials constitute the final bases to introduce new radionuclides for RSV.Curves displaying absorbed dose as a function of distance into the diseased synovium have been generated for each of the six beta-emitting radionuclides investigated (<a href="#fig1" class="elsevierStyleCrossRefs">figura 1</a>). Having selected the appropriated radionuclide, these curves can then be used by the clinician to predict the amount of activity required to deliver sufficient dose to a given synovial depth.<a name="fig1" class="elsevierStyleCrossRefs"></a><img src="125v28n04-13140119fig1.jpg" alt="Absorbed doses profiles (Gy*cm2/h*MBq) as a function of distance into the diseased synovium."></img>Fig. 1. Absorbed doses profiles (Gy*cm2/h*MBq) as a function of distance into the diseased synovium.Articular cartilageThe presence of the healthy articular cartilage in the arthritic joint limits the prescribed treatment activity. The question of harmful effect of β radiation in the articular cartilage has always been a subject of debate. According to Johnson et al<a href="#bib9" class="elsevierStyleCrossRefs">9</a>, for a cartilage thickness of 2mm. a dose of 1Gy is reached at a depth of 1.5mm in the adjoining bone with 185MBq of 90Y. Thus, the β radiation induces no systemic effect. Absorbed doses profiles in the articular cartilage versus distance are presented in <a href="#fig2" class="elsevierStyleCrossRefs">figura 2</a>.<a name="fig2" class="elsevierStyleCrossRefs"></a><img src="125v28n04-13140119fig2.jpg" alt="Absorbed doses profiles (Gy*cm2/h*MBq) as a function of distance into the articular cartilage."></img>Fig. 2. Absorbed doses profiles (Gy*cm2/h*MBq) as a function of distance into the articular cartilage.Results presented in this paper are in agreement whit those found in the references <a href="#bib9" class="elsevierStyleCrossRefs">9</a>,<a href="#bib10" class="elsevierStyleCrossRefs">10</a>,<a href="#bib11" class="elsevierStyleCrossRefs">11</a>,<a href="#bib17" class="elsevierStyleCrossRefs">17</a>,<a href="#bib18" class="elsevierStyleCrossRefs">18</a>.ConclusionsIn RSV, the radionuclide choice is critical since the synovial thickness of different joints in the human body (e.g., finger, wrist, knee, etc.) vary substantially. Also, joints at different stages of the disease show different degrees of swelling and may also call for a beta emitter of different penetration. Each patient should have a MRI study prior to RSV in order to determine the tissue volume and to select the appropriated dose and radionuclides to be used, eliminating the practice of fixed radionuclides and doses for the treatment of different kind of joints, methodology applied in many clinics in Europe<a href="#bib19" class="elsevierStyleCrossRefs">19</a>,<a href="#bib20" class="elsevierStyleCrossRefs">20</a>. The selection of the radionuclide for the treatment will depend on the thickness of the synovium to be treated and the proximity of the non target organs to the joint (bone and articular cartilage). Values here presented can be a useful tool to prescribe adequate quantities of new radionuclides for RSV. Additionally, provide information about the radiation damage to articular cartilage." "pdfFichero" => "125v28n04a13140119pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec231864" "palabras" => array:5 [ 0 => "Arthritis" 1 => "Rheumatoid" 2 => "Synovial membrane" 3 => "Monte Carlo method" 4 => "Radiation effects" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "El principal objetivo de este trabajo fue obtener los perfiles de dosis para los radionúclidos de uso frecuente en radiosinoviortesis. Estos perfiles revelan la dosis absorbida impartida por unidad de actividad del radionúclido inyectado (Gy/h*MBq) en la membrana sinovial y el cartílago articular. Los radionúclidos seleccionados fueron 32P, 90Y, 188Re, 177Lu, 153Sm and 169Er. También fue calculado el rango terapéutico de cada radionúclido en el tejido sinovial. Este rango determina el grosor synovial que puede ser irradiado suficientemente y por lo tanto, tratado con éxito. Los valores S para la membrana sinovial y el cartílago articular fueron calculados usando como modelo un cilindro con la fuente distribuida uniformemente en su volumen. La membrana sinovial fue simulada variando el radio del cilindro (rango 0.5cm–9cm) y su altura (rango 0.01cm–0.04cm). La variación del radio del cilindro representa varios tamaños de superficie sinovial (articulaciones pequeñas, medianas y grandes), y se define como el área de la base del cilindro; la variación de la altura, representa diferentes estados de progresión de la artritis reumatoide. El mismo modelo fue empleado para la simulación del cartílago articular, pero la fuente fue uniformemente distribuida dentro de una capa cilíndrica (0.01cm) y 1cm de radio. Los resultados obtenidos permiten la estimación de la dosis que será entregada a la membrana sinovial y el cartílago articular para diferentes tamaños de articulación y diferentes estados de progresión de la artritis reumática." ] "en" => array:1 [ "resumen" => "The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose per activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were 32P, 90Y, 188Re, 177Lu, 153Sm and 169Er. The therapeutic range of each radionuclides in synovial tissue were also calculated. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume. The synovial membrane was simulated varying the radius of the cylinder (from 0.5cm to 9cm) and its height (from 0.01cm to 0.04cm). The area in the base of the cylinder represents different sizes of the synovial surface (small, medium and large joints). The height of the cylinder represents different stages of the progression of the rheumatoid arthritis. The same model was used to simulate the articular cartilage but, the source was uniformly distributed into a cylindrical slab (0.01cm height and 1cm of radius. The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis (RA)." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v28n04-13140119fig1.jpg" "Alto" => 1284 "Ancho" => 1632 "Tamanyo" => 222438 ] ] "descripcion" => array:1 [ "en" => "Absorbed doses profiles (Gy*cm 2/h*MBq) as a function of distance into the diseased synovium." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "125v28n04-13140119fig2.jpg" "Alto" => 1281 "Ancho" => 1632 "Tamanyo" => 208570 ] ] "descripcion" => array:1 [ "en" => "Absorbed doses profiles (Gy*cm 2/h*MBq) as a function of distance into the articular cartilage." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Merck Manual, 17.a Edición 1999." 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Absorbed dose profiles for 32P, 90Y, 188Re, 177Lu, 153Sm and 169Er: radionuclides used in radiosynoviortheses treatment

Perfiles de dosis absorbida para 32P, 90Y, 188Re, 177Lu, 153Sm y 169Er : radionuclidos usados en el tratamiento de radiosinoviortesis

M.. Torresa, E.. Ayraa, O.. Albuernea, M.A.. Montano Delgadob

a Radiation Protection Department, Isotopes Centre, Carretera la Rada, Km 3 1/2 Havana, Cuba

b Hospital General Docente Enrique Cabrera, Havana, Cuba

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    "titulo" => "Absorbed dose profiles for <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm and <span class="elsevierStyleSup">169</span>Er&#58; radionuclides used in radiosynoviortheses treatment"
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        "titulo" => "Perfiles de dosis absorbida para <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm y <span class="elsevierStyleSup">169</span>Er <span class="elsevierStyleBold">&#58;</span> radionuclidos usados en el tratamiento de radiosinoviortesis"
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          "en" => "Absorbed doses profiles &#40;Gy&#42;cm <span class="elsevierStyleSup">2</span>&#47;h&#42;MBq&#41; as a function of distance into the diseased synovium&#46;"
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    "textoCompleto" => "<span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara">The treatment of inflammatory arthropathies is aimed to diminish the inflammation&#44; relieve the pain&#44; improve the functional capability and induce the remission of the disease&#46; Although every case requires specific therapeutic guidelines<a href="&#35;bib1" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a>&#44; some joints may not experience clinical improvement&#44; so other complementary therapies should be used&#46; Most commons are intrarticular corticoids&#44; chemical synovectomy&#44; surgical synovectomy and radiosynoviortheses &#40;RSV&#41;&#46; An alternative to surgery is RSV&#44; which eliminates the inflamed tissue by means of beta radiation&#46; The first published reports of this last treatment are as back as to 1924<a href="&#35;bib2" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a>&#46; In the clinical practice&#44; the first results were published in 1952<a href="&#35;bib3" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a> and were followed in the 60s with the inclusion of Y-90<a href="&#35;bib4" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib5" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a>&#46;</p><p class="elsevierStylePara">The RSV is the injection of a radioactive substance inside any synovial cavity&#44; in such way that the injected radionuclide makes contact with the synovial membrane&#46; This substance is rapidly phagocytized by the synovial lining cells&#46; During the radioactive decay of the injected radionuclide&#44; a therapeutic dose will be delivered to the synovial tissue destroying it&#46; The energy of the beta emitters used in radiosynoviortheses range from 0&#46;34MeV &#40;0&#46;33mm penetration in tissue&#41; in the case of Er-169 to 2&#46;27MeV &#40;3&#46;6mm penetration in tissue&#41; for the Y-90&#46; The half life of these isotopes goes from 2&#46;3 hrs &#40;Dy-165&#41; to 27&#46;8 days &#40;Cr-51&#41;<a href="&#35;bib6" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a>&#46; Nowadays&#44; the selection of the radionuclide to be used depends on the size of the joint to be treated&#46; Thus&#44; the smaller the joint&#44; the lower should be the energy and therefore the penetration&#46; These facts led to the use of fixed radionuclides for specific joints&#46; The first works on the assessment of doses to the patients in RSV were published in the 80s and early 90s<a href="&#35;bib7" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib9" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a>&#46; As new radiopharmaceuticals offering many potential advantages for RSV are being developed in our centre&#44; it seems prudent to evaluate the dose distribution of some radionuclides that have been used or tested in animal and human models&#58; <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">186</span>Re <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm and <span class="elsevierStyleSup">169</span>Er&#46;</p><p class="elsevierStylePara">The method used to assess the dosimetry in RSV is known as the Monte Carlo method&#46; Nevertheless&#44; while it provides an improved technique for calculating local dosimetry&#44; there are still clear difficulties involved in relating this dosimetry to clinical outcome&#46; Although the goal of radiation synovectomy procedure is ablation of the inflamed synovial tissue&#44; very few studies have been performed to determine the dose required to reach this goal&#46; The rationale for choosing a particular administered dose of a given isotope for a given joint is obscure&#46; As with other form of therapy&#44; clinical success in RSV will depend on the thickness of the synovium to be treated and the proximity of the non target organs to the joint &#40;bone and articular cartilage&#41;&#44; so it will be based in the absorbed dose and the penetration of the radiation emitted by the radionuclide&#46;</p><p class="elsevierStylePara">The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses&#46; These profiles reveal the absorbed dose per activity of injected radionuclide &#40;Gy&#47;h&#42;MBq&#41; in the synovial membrane and the articular cartilage&#46; The radionuclides involved were those previously mentioned&#46; The therapeutic range of each radionuclides in synovial tissue were also calculated&#46; The therapeutic range is defined as the deepness at which the absorbed dose equals the 10&#37; of the maximum dose deposited in the synovial surface&#46; This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated&#46;</p><span class="elsevierStyleSectionTitle">Materials and methods</span><p class="elsevierStylePara">The synovial joint is basically the articular cartilage&#44; bone and tissue &#40;synovial membrane&#41;&#46; In <a href="&#35;tbl1" class="elsevierStyleCrossRefs">tabla 1</a> is shown the composition and density of every constituent according to Johnson and Yanch<a href="&#35;bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a>&#46;</p><p class="elsevierStylePara">Table 1&#46; Composition and density of components of the synovial joint</p><a name="tbl1" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Elements</td><td>H</td><td>C</td><td>N</td><td>O</td><td>Na</td><td>Mg</td><td>P</td><td>S</td><td>Ca</td><td>Cl</td><td><span class="elsevierStyleItalic">&#961;</span> &#40;g&#47;cm<span class="elsevierStyleSup">3</span>&#41;</td></tr><tr align="left"><td>Bone &#40;&#37;&#41;</td><td>3&#46;4</td><td>15&#46;5</td><td>4&#46;2</td><td>43&#46;5</td><td>0&#46;1</td><td>0&#46;2</td><td>10&#46;3</td><td>0&#46;3</td><td>22&#46;5</td><td>&#8211;</td><td>1&#46;92</td></tr><tr align="left"><td>Articular cartilage &#40;&#37;&#41;</td><td>9&#46;6</td><td>9&#46;9</td><td>2&#46;2</td><td>74&#46;4</td><td>0&#46;5</td><td>&#8211;</td><td>2&#46;2</td><td>0&#46;9</td><td>&#8211;</td><td>0&#46;3</td><td>1&#46;1</td></tr><tr align="left"><td>Tissue &#40;&#37;&#41;</td><td>10&#46;0</td><td>14&#46;9</td><td>3&#46;5</td><td>71&#46;6</td><td>&#8211;</td><td>&#8211;</td><td>&#8211;</td><td>&#8211;</td><td>&#8211;</td><td>&#8211;</td><td>1&#46;0</td></tr></table><p class="elsevierStylePara">The energy of beta particles used in RSV should be enough as to deliver a dose of radiation good for destroying the synovial tissue and yet not as high as to expose unnecessarily the cartilage and bone&#46; In <a href="&#35;tbl2" class="elsevierStyleCrossRefs">tabla 2</a> are listed the energetic characteristics of the radionuclides assessed in this work&#46;</p><p class="elsevierStylePara">Table 2&#46; Energetic characteristic of the assessed radionuclides</p><a name="tbl2" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Radionuclides</td><td>Y-90</td><td>P-32</td><td>Re-188</td><td>Lu-177</td><td>Sm-153</td><td>Er-169</td></tr><tr align="left"><td><span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1&#47;2</span></td><td>64&#46;1h</td><td>14&#46;3 days</td><td>16&#46;98h</td><td>6&#46;71 days</td><td>46&#46;7h</td><td>9&#46;4 days</td></tr><tr align="left"><td>Emission type</td><td>Beta</td><td>Beta</td><td>Beta&#44; gamma&#44; electron</td><td>Beta&#44; gamma&#44; electron</td><td>Beta&#44; gamma&#44; electron</td><td>Beta&#44; gamma&#44; electron</td></tr></table><p class="elsevierStylePara">The MCNP4C Monte Carlo code was used to perform the dosimetry calculations&#46; MCNP is a general-purpose Monte Carlo N-Particle code that can be used for neutron&#44; photon&#44; electron&#44; or coupled neutron&#47;photon&#47;electron transport&#46; MCNP4C is the first major release of MCNP since version 4B<a href="&#35;bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a>&#46; The beta spectrum of the radionuclides listed in <a href="&#35;tbl2" class="elsevierStyleCrossRefs">tabla 2</a> was downloaded from  www&#46;doseinfo-radar  <a href="&#35;bib12" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">12</span></a> and the characteristics of the gamma and&#47;or electronic emission are the ones in the software Radiation Decay<a href="&#35;bib13" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a>&#46;</p><p class="elsevierStylePara">To determine the therapeutic range &#40;X<span class="elsevierStyleInf">90</span>&#41;&#44; an isotropic point source was simulated in the centre of various concentric spheres of different radii&#46; These radii ranged from 1mm to 10mm &#40;increasing 1mm at a time&#41; for all radionuclides but for Er-169&#46; In this case&#44; the radii ranged from 0&#46;1mm to 1mm &#40;0&#46;1mm at a time&#41;&#46;</p><p class="elsevierStylePara">The <span class="elsevierStyleItalic">S</span> values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume&#46; The synovial membrane was simulated varying the radius of the cylinder &#40;from 0&#46;5cm to 9cm&#41; and its height &#40;from 0&#46;01cm to 0&#46;04cm&#41;&#46; The area in the base of the cylinder represents different sizes of the synovial surface &#40;small&#44; medium and large joints&#41;&#46; The synovium area can be estimated through computer tomography &#40;CT&#41;<a href="&#35;bib7" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a>&#46; The height of the cylinder represents different stages of the progression of the rheumatoid arthritis &#40;RA&#41;<a href="&#35;bib8" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a>&#46; The same model was used to simulate the articular cartilage but&#44; the source was uniformly distributed into a cylindrical slab &#40;0&#46;01cm height and 1cm of radius&#41;&#46; The S value as a function of distance into the diseased synovium and articular cartilage for each of the 6 beta emitting radionuclides mentioned earlier were simulated incorporating very thin cylindrical slabs of tissue and articular cartilage to the original model&#46;</p><p class="elsevierStylePara">   S     &#61;       E       m       &#42;     576&#46;7     &#42;     1       0        -     3     </p><p class="elsevierStylePara">The S &#40;Gy&#47;h&#42;MBq&#41; values have been calculated for different pair of source-target organs and for some radionuclides of interest in Nuclear Medicine<a href="&#35;bib14" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">14</span></a>&#46; In this paper&#44; using Monte Carlo computer calculations&#44; the S values for each proposed model were obtained calculating the mean absorbed energy &#40;<span class="elsevierStyleItalic">E</span>&#41; per disintegration deposited in a target mass &#40;synovial membrane and articular cartilage&#41;&#44; divided by the tissue mass &#40;<span class="elsevierStyleItalic">m</span>&#41; and multiplied by 576&#46;7E-03 to obtain the absorbed dose level per cumulated activity in the source region&#44; Gy&#47;h&#42;MBq&#46; The basic equation for this situation is&#58;where <span class="elsevierStyleItalic">m</span>&#58; tissue mass &#40;g&#41;&#44; <span class="elsevierStyleItalic">E</span>&#58; mean absorbed energy &#40;<span class="elsevierStyleItalic">E</span>&#41; per disintegration deposited in a target mass &#40;MeV&#41;&#46;</p><p class="elsevierStylePara">     D       t       &#61;     S     &#215;     1&#46;44     &#215;       T        1     &#47;     2     f        &#305;      &#180;       sico        &#215;       A        o     </p><p class="elsevierStylePara">If we consider that the radionuclide decays completely in the joint&#44; so no leakage effect is taken into account&#44; important aspect to keep in mind&#44; the dose absorbed in the synovial membrane is obtained through the Eq&#46; <a href="&#35;eq2" class="elsevierStyleCrossRefs"></a>&#46;where <span class="elsevierStyleItalic">S</span>&#58; <span class="elsevierStyleItalic">S</span>-value &#40;Gy&#47;h&#42;MBq&#41;&#44; <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1&#47;2</span>&#58; half life&#44; <span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">0</span>&#58; injected activity into the articular cavity&#46;</p><p class="elsevierStylePara">For all cases&#44; a sufficient number of electron and photon transport histories were generated to produce statistically reliable energy tallies&#44; with relative errors less than 0&#46;10&#46; Also&#44; the Bremsstrahlung radiation was considered in the calculations&#46;</p><span class="elsevierStyleSectionTitle">Analysis and discussion of results</span><span class="elsevierStyleSectionTitle">Synovial membrane</span><p class="elsevierStylePara"><span class="elsevierStyleItalic">S</span>-values for synovial membranes with different synovium size are shown in <a href="&#35;tbl3" class="elsevierStyleCrossRefs">tabla 3</a>&#46; As the area of the inflamed synovium increases&#44; diminishes the value of the absorbed dose rate in the synovial membrane&#46; Studies with <span class="elsevierStyleSup">90</span>Y usually apply an average administered activity of 185MBq for arthritic knee patients with synovium area of 250cm<span class="elsevierStyleSup">2</span>&#46; This value of administered activity will deliver approximately 130Gy in the synovial membrane according to our model &#40;<span class="elsevierStyleItalic">S</span>-value&#61;0&#46;007&#41;&#46; If we wish to obtain the same therapeutic effect in the synovial membrane of an arthritic wrist with 50cm<span class="elsevierStyleSup">2</span> of synovium area &#40;<span class="elsevierStyleItalic">S</span>-value&#61;0&#46;035&#41;&#44; it only will be necessary to inject 37MBq of <span class="elsevierStyleSup">90</span>Y&#46; In this case it is considered that the radionuclide decays completely in the joint &#40;Eq&#46; <a href="&#35;eq2" class="elsevierStyleCrossRefs"></a>&#41;&#46;</p><p class="elsevierStylePara">Table 3&#46; <span class="elsevierStyleItalic">S</span>-Values &#40;Gy&#47;MBq&#42;h&#41; for different synovium sizes and thickness of synovial lining cells&#46;</p><a name="tbl3" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>A&#40;cm<span class="elsevierStyleSup">2</span>&#41;</td><td rowspan="0" colspan="12">Thickness of synovial lining cells</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td></td><td rowspan="0" colspan="6">0&#46;01cm</td><td rowspan="0" colspan="6">0&#46;015cm</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td></td><td><span class="elsevierStyleSup">90</span>Y</td><td><span class="elsevierStyleSup">32</span>P</td><td><span class="elsevierStyleSup">188</span>Re</td><td><span class="elsevierStyleSup">177</span>Lu</td><td><span class="elsevierStyleSup">153</span>Sm</td><td><span class="elsevierStyleSup">169</span>Er</td><td><span class="elsevierStyleSup">90</span>Y</td><td><span class="elsevierStyleSup">32</span>P</td><td><span class="elsevierStyleSup">188</span>Re</td><td><span class="elsevierStyleSup">177</span>Lu</td><td><span class="elsevierStyleSup">153</span>Sm</td><td><span class="elsevierStyleSup">169</span>Er</td></tr><tr align="left"><td>13</td><td>0&#46;152</td><td>0&#46;154</td><td>0&#46;325</td><td>0&#46;335</td><td>0&#46;294</td><td>0&#46;295</td><td>0&#46;144</td><td>0&#46;146</td><td>0&#46;291</td><td>0&#46;277</td><td>0&#46;243</td><td>0&#46;240</td></tr><tr align="left"><td>20</td><td>0&#46;098</td><td>0&#46;099</td><td>0&#46;208</td><td>0&#46;214</td><td>0&#46;188</td><td>0&#46;189</td><td>0&#46;092</td><td>0&#46;094</td><td>0&#46;186</td><td>0&#46;177</td><td>0&#46;156</td><td>0&#46;154</td></tr><tr align="left"><td>28</td><td>0&#46;068</td><td>0&#46;069</td><td>0&#46;145</td><td>0&#46;149</td><td>0&#46;131</td><td>0&#46;131</td><td>0&#46;064</td><td>0&#46;065</td><td>0&#46;130</td><td>0&#46;123</td><td>0&#46;108</td><td>0&#46;107</td></tr><tr align="left"><td>38</td><td>0&#46;050</td><td>0&#46;051</td><td>0&#46;106</td><td>0&#46;109</td><td>0&#46;096</td><td>0&#46;096</td><td>0&#46;047</td><td>0&#46;048</td><td>0&#46;095</td><td>0&#46;091</td><td>0&#46;080</td><td>0&#46;078</td></tr><tr align="left"><td>50</td><td>0&#46;038</td><td>0&#46;039</td><td>0&#46;081</td><td>0&#46;084</td><td>0&#46;074</td><td>0&#46;074</td><td>0&#46;036</td><td>0&#46;037</td><td>0&#46;073</td><td>0&#46;069</td><td>0&#46;061</td><td>0&#46;060</td></tr><tr align="left"><td>64</td><td>0&#46;030</td><td>0&#46;031</td><td>0&#46;064</td><td>0&#46;066</td><td>0&#46;058</td><td>0&#46;058</td><td>0&#46;029</td><td>0&#46;029</td><td>0&#46;058</td><td>0&#46;055</td><td>0&#46;048</td><td>0&#46;047</td></tr><tr align="left"><td>79</td><td>0&#46;024</td><td>0&#46;025</td><td>0&#46;052</td><td>0&#46;054</td><td>0&#46;047</td><td>0&#46;047</td><td>0&#46;023</td><td>0&#46;024</td><td>0&#46;047</td><td>0&#46;044</td><td>0&#46;039</td><td>0&#46;038</td></tr><tr align="left"><td>95</td><td>0&#46;020</td><td>0&#46;020</td><td>0&#46;043</td><td>0&#46;044</td><td>0&#46;039</td><td>0&#46;039</td><td>0&#46;019</td><td>0&#46;019</td><td>0&#46;039</td><td>0&#46;037</td><td>0&#46;032</td><td>0&#46;032</td></tr><tr align="left"><td>113</td><td>0&#46;017</td><td>0&#46;017</td><td>0&#46;036</td><td>0&#46;037</td><td>0&#46;033</td><td>0&#46;033</td><td>0&#46;016</td><td>0&#46;016</td><td>0&#46;032</td><td>0&#46;031</td><td>0&#46;027</td><td>0&#46;027</td></tr><tr align="left"><td>133</td><td>0&#46;014</td><td>0&#46;015</td><td>0&#46;031</td><td>0&#46;032</td><td>0&#46;028</td><td>0&#46;028</td><td>0&#46;014</td><td>0&#46;014</td><td>0&#46;028</td><td>0&#46;026</td><td>0&#46;023</td><td>0&#46;023</td></tr><tr align="left"><td>154</td><td>0&#46;013</td><td>0&#46;013</td><td>0&#46;027</td><td>0&#46;027</td><td>0&#46;024</td><td>0&#46;024</td><td>0&#46;012</td><td>0&#46;012</td><td>0&#46;024</td><td>0&#46;023</td><td>0&#46;020</td><td>0&#46;020</td></tr><tr align="left"><td>177</td><td>0&#46;011</td><td>0&#46;011</td><td>0&#46;023</td><td>0&#46;024</td><td>0&#46;021</td><td>0&#46;021</td><td>0&#46;010</td><td>0&#46;010</td><td>0&#46;021</td><td>0&#46;020</td><td>0&#46;017</td><td>0&#46;017</td></tr><tr align="left"><td>201</td><td>0&#46;010</td><td>0&#46;010</td><td>0&#46;020</td><td>0&#46;021</td><td>0&#46;018</td><td>0&#46;018</td><td>0&#46;009</td><td>0&#46;009</td><td>0&#46;018</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;015</td></tr><tr align="left"><td>227</td><td>0&#46;008</td><td>0&#46;009</td><td>0&#46;018</td><td>0&#46;019</td><td>0&#46;016</td><td>0&#46;016</td><td>0&#46;008</td><td>0&#46;008</td><td>0&#46;016</td><td>0&#46;015</td><td>0&#46;013</td><td>0&#46;013</td></tr><tr align="left"><td>254</td><td>0&#46;008</td><td>0&#46;008</td><td>0&#46;016</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;015</td><td>0&#46;007</td><td>0&#46;007</td><td>0&#46;014</td><td>0&#46;014</td><td>0&#46;012</td><td>0&#46;012</td></tr><tr align="left"><td></td></tr><tr align="left"><td></td><td>0&#46;02cm</td><td>0&#46;025cm</td></tr><tr align="left"><td>A&#40;cm<span class="elsevierStyleSup">2</span>&#41;</td><td><span class="elsevierStyleSup">90</span>Y</td><td><span class="elsevierStyleSup">32</span>P</td><td><span class="elsevierStyleSup">188</span>Re</td><td><span class="elsevierStyleSup">177</span>Lu</td><td><span class="elsevierStyleSup">153</span>Sm</td><td><span class="elsevierStyleSup">169</span>Er</td><td><span class="elsevierStyleSup">90</span>Y</td><td><span class="elsevierStyleSup">32</span>P</td><td><span class="elsevierStyleSup">188</span>Re</td><td><span class="elsevierStyleSup">177</span>Lu</td><td><span class="elsevierStyleSup">153</span>Sm</td><td><span class="elsevierStyleSup">169</span>Er</td></tr><tr align="left"><td>13</td><td>0&#46;138</td><td>0&#46;140</td><td>0&#46;264</td><td>0&#46;237</td><td>0&#46;211</td><td>0&#46;197</td><td>0&#46;134</td><td>0&#46;136</td><td>0&#46;244</td><td>0&#46;207</td><td>0&#46;189</td><td>0&#46;166</td></tr><tr align="left"><td>20</td><td>0&#46;089</td><td>0&#46;090</td><td>0&#46;170</td><td>0&#46;151</td><td>0&#46;135</td><td>0&#46;126</td><td>0&#46;086</td><td>0&#46;087</td><td>0&#46;156</td><td>0&#46;132</td><td>0&#46;121</td><td>0&#46;106</td></tr><tr align="left"><td>28</td><td>0&#46;062</td><td>0&#46;063</td><td>0&#46;118</td><td>0&#46;105</td><td>0&#46;094</td><td>0&#46;088</td><td>0&#46;060</td><td>0&#46;061</td><td>0&#46;109</td><td>0&#46;092</td><td>0&#46;084</td><td>0&#46;074</td></tr><tr align="left"><td>38</td><td>0&#46;045</td><td>0&#46;046</td><td>0&#46;087</td><td>0&#46;077</td><td>0&#46;069</td><td>0&#46;064</td><td>0&#46;044</td><td>0&#46;045</td><td>0&#46;080</td><td>0&#46;068</td><td>0&#46;062</td><td>0&#46;054</td></tr><tr align="left"><td>50</td><td>0&#46;035</td><td>0&#46;035</td><td>0&#46;066</td><td>0&#46;059</td><td>0&#46;053</td><td>0&#46;049</td><td>0&#46;034</td><td>0&#46;034</td><td>0&#46;061</td><td>0&#46;052</td><td>0&#46;047</td><td>0&#46;042</td></tr><tr align="left"><td>64</td><td>0&#46;028</td><td>0&#46;028</td><td>0&#46;056</td><td>0&#46;047</td><td>0&#46;042</td><td>0&#46;039</td><td>0&#46;027</td><td>0&#46;027</td><td>0&#46;048</td><td>0&#46;041</td><td>0&#46;037</td><td>0&#46;033</td></tr><tr align="left"><td>79</td><td>0&#46;022</td><td>0&#46;023</td><td>0&#46;043</td><td>0&#46;038</td><td>0&#46;034</td><td>0&#46;032</td><td>0&#46;022</td><td>0&#46;022</td><td>0&#46;039</td><td>0&#46;033</td><td>0&#46;030</td><td>0&#46;027</td></tr><tr align="left"><td>95</td><td>0&#46;018</td><td>0&#46;019</td><td>0&#46;035</td><td>0&#46;031</td><td>0&#46;028</td><td>0&#46;026</td><td>0&#46;018</td><td>0&#46;018</td><td>0&#46;032</td><td>0&#46;027</td><td>0&#46;025</td><td>0&#46;022</td></tr><tr align="left"><td>113</td><td>0&#46;016</td><td>0&#46;016</td><td>0&#46;030</td><td>0&#46;026</td><td>0&#46;024</td><td>0&#46;022</td><td>0&#46;015</td><td>0&#46;015</td><td>0&#46;027</td><td>0&#46;023</td><td>0&#46;021</td><td>0&#46;018</td></tr><tr align="left"><td>133</td><td>0&#46;013</td><td>0&#46;013</td><td>0&#46;025</td><td>0&#46;022</td><td>0&#46;020</td><td>0&#46;019</td><td>0&#46;013</td><td>0&#46;013</td><td>0&#46;023</td><td>0&#46;020</td><td>0&#46;018</td><td>0&#46;016</td></tr><tr align="left"><td>154</td><td>0&#46;011</td><td>0&#46;012</td><td>0&#46;022</td><td>0&#46;019</td><td>0&#46;017</td><td>0&#46;016</td><td>0&#46;011</td><td>0&#46;011</td><td>0&#46;020</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;014</td></tr><tr align="left"><td>177</td><td>0&#46;010</td><td>0&#46;010</td><td>0&#46;019</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;014</td><td>0&#46;010</td><td>0&#46;010</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;013</td><td>0&#46;012</td></tr><tr align="left"><td>201</td><td>0&#46;009</td><td>0&#46;009</td><td>0&#46;017</td><td>0&#46;015</td><td>0&#46;013</td><td>0&#46;012</td><td>0&#46;008</td><td>0&#46;009</td><td>0&#46;015</td><td>0&#46;013</td><td>0&#46;012</td><td>0&#46;010</td></tr><tr align="left"><td>227</td><td>0&#46;008</td><td>0&#46;008</td><td>0&#46;015</td><td>0&#46;013</td><td>0&#46;012</td><td>0&#46;011</td><td>0&#46;007</td><td>0&#46;008</td><td>0&#46;014</td><td>0&#46;011</td><td>0&#46;010</td><td>0&#46;009</td></tr><tr align="left"><td>254</td><td>0&#46;007</td><td>0&#46;007</td><td>0&#46;013</td><td>0&#46;012</td><td>0&#46;010</td><td>0&#46;010</td><td>0&#46;007</td><td>0&#46;007</td><td>0&#46;012</td><td>0&#46;010</td><td>0&#46;009</td><td>0&#46;008</td></tr></table><p class="elsevierStylePara">Since electron emission energies and spectral shapes differ between &#946;-active radionuclides&#44; the absorbed dose penetration range can vary substantially from one radionuclide to another&#46; Essentially&#44; this effective penetration ranges determine the thickness of inflamed synovium that can be treated successfully&#46; One way of evaluating this range is to establish the distance at which the absorbed dose equals the 10&#37; of the dose deposited in the synovial membrane &#40;X<span class="elsevierStyleInf">90</span>&#41;&#46; The X<span class="elsevierStyleInf">90</span> values for each of the six beta-emitting radionuclides considered in this paper are included in <a href="&#35;tbl4" class="elsevierStyleCrossRefs">tabla 4</a>&#46;</p><p class="elsevierStylePara">Table 4&#46; Therapeutic range &#40;X<span class="elsevierStyleInf">90</span>&#41; for <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm&#44; and <span class="elsevierStyleSup">169</span>Er</p><a name="tbl4" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td rowspan="0" colspan="6">X<span class="elsevierStyleInf">90</span> &#40;mm&#41;</td><td></td><td></td><td></td><td></td><td></td></tr><tr align="left"><td><span class="elsevierStyleSup">90</span>Y</td><td><span class="elsevierStyleSup">32</span>P2</td><td><span class="elsevierStyleSup">188</span>Re</td><td><span class="elsevierStyleSup">177</span>Lu</td><td><span class="elsevierStyleSup">153</span>Sm</td><td><span class="elsevierStyleSup">169</span>Er</td></tr><tr align="left"><td>2&#46;22</td><td>2&#46;1</td><td>2&#46;1</td><td>1&#46;3</td><td>1&#46;6</td><td>0&#46;18</td></tr></table><p class="elsevierStylePara">Note that X<span class="elsevierStyleInf">90</span> can be divided in three groups&#46; The first group formed by <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">32</span>P and <span class="elsevierStyleSup">188</span>Re with X<span class="elsevierStyleInf">90</span>&#61;2mm&#44; the second group &#40;<span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span>Sm&#41; with 1&#38;&#35;60&#59;X<span class="elsevierStyleInf">90</span>&#38;&#35;60&#59;&#61;2mm and the third one &#40;<span class="elsevierStyleSup">169</span>Er&#41;&#59; X<span class="elsevierStyleInf">90</span>&#38;&#35;60&#59;1&#46; These variations can be used to help the clinician performing RSV in selecting the best radionuclide for individual joint and synovium condition&#46; No single radionuclide is ideally suited for use in every radiation synovectomy&#44; since the thickness of inflamed synovium will differ from joint to joint and from patient to patient&#46; In a large joint with thick synovial membrane&#44; for example&#44; deep penetration of the beta particles is desirable in order to sufficiently treat the inflamed tissue&#46; In small joints with thin synovial membrane&#44; this penetration represents an unnecessary radiation hazard to other normal structures around the joint&#46;</p><p class="elsevierStylePara">For example&#44; for an arthritic knee&#44; with thick synovium&#44; the suited radionuclides to deliver a therapeutic dose in the synovial depth are <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">32</span>P and <span class="elsevierStyleSup">188</span>Re&#46; An average administered activity of 185MBq of <span class="elsevierStyleSup">90</span>Y delivers a radiation absorbed dose of approximately 100Gy to 100 g-synovium&#46; Since this dose of <span class="elsevierStyleSup">90</span>Y was shown to be efficacious in the treatment<a href="&#35;bib15" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a>&#44; other investigators have used a &#8220;calculated <span class="elsevierStyleSup">90</span>Y dose equivalent&#8221; when administering other radionuclide&#46;</p><p class="elsevierStylePara">The <a href="&#35;tbl5" class="elsevierStyleCrossRefs">tabla 5</a> shows activity values of <span class="elsevierStyleSup">188</span>Re and <span class="elsevierStyleSup">32</span>P to obtain the &#8220;<span class="elsevierStyleSup">90</span>Y dose equivalent&#8221; in the synovial membrane &#40;0&#46;2mm thickness of synovial lining cells and 250cm<span class="elsevierStyleSup">2</span> of synovium area&#41;&#46;</p><p class="elsevierStylePara">Table 5&#46; Values of activity administered of <span class="elsevierStyleSup">188</span>Re and <span class="elsevierStyleSup">32</span>P to obtain the &#8220;<span class="elsevierStyleSup">90</span>Y dose equivalent&#8221; into the synovial membrane</p><a name="tbl5" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Radionuclide</td><td>X<span class="elsevierStyleInf">90</span></td><td><span class="elsevierStyleItalic">S</span>-value Gy&#47;h&#42;MBq</td><td>Absorbed dose &#40;Gy&#41;</td><td>Administered activity &#40;MBq&#41;</td></tr><tr align="left"><td>Y-90</td><td>2&#46;22</td><td>0&#46;007</td><td>130</td><td>185</td></tr><tr align="left"><td>P-32</td><td>2&#46;1</td><td>0&#46;007</td><td>130</td><td>37</td></tr><tr align="left"><td>Re-188</td><td>2&#46;1</td><td>0&#46;013</td><td>130</td><td>407</td></tr></table><p class="elsevierStylePara">Note the great differences in the activity administered&#44; but not in the effective penetration ranges in tissue&#46; In this case the radionuclide selection to treat the damaged tissue will depend on its availability&#46; <span class="elsevierStyleSup">32</span>P and <span class="elsevierStyleSup">90</span>Y are the two isotopes most widely used today as the basis for RSV agents&#59; however&#44; these isotopes do not emit imageable gamma rays and thus are very difficult to obtain quantitative dosimetric information on patients treated with agents based on <span class="elsevierStyleSup">32</span>P and <span class="elsevierStyleSup">90</span>Y&#46; These radionuclides are available in our centre&#46; <span class="elsevierStyleSup">188</span>Re has the advantage of a tissue penetration equivalent to that of <span class="elsevierStyleSup">90</span>Y but a shorter half-life&#44; important for leakage reduction<a href="&#35;bib16" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">16</span></a>&#46; It has a 155keV gamma ray&#44; which would permit analysis of leakage to other organs by gamma camera imaging&#46; The possibility of producing the isotope with an <span class="elsevierStyleSup">188</span>W-<span class="elsevierStyleSup">188</span>Re generator would greatly extend its availability&#46;</p><p class="elsevierStylePara">Following the same procedure previously described with <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">32</span>P and <span class="elsevierStyleSup">188</span>Re in median and small joints with thin synovium depth&#44; the most appropriate radionuclides are those with less X<span class="elsevierStyleInf">90</span>&#46; The <a href="&#35;tbl6" class="elsevierStyleCrossRefs">tabla 6</a> shows the activity values of <span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span>Sm to obtain the &#8220;<span class="elsevierStyleSup">90</span>Y dose equivalent&#8221; in the synovial membrane of an arthritic wrist&#46;</p><p class="elsevierStylePara">Table 6&#46; Values of activity administered of <span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span> Sm to obtain the &#8220;<span class="elsevierStyleSup">90</span>Y dose equivalent&#8221; into the synovial membrane of an arthritics wrist &#40;0&#46;1mm thickness of the synovial membrane and 50cm<span class="elsevierStyleSup">2</span> of synovium area&#41;</p><a name="tbl6" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Radionuclide</td><td>X<span class="elsevierStyleInf">90</span></td><td><span class="elsevierStyleItalic">S</span>-value Gy&#47;h&#42;MBq</td><td>Absorbed dose &#40;Gy&#41;</td><td>Administered activity &#40;MBq&#41;</td></tr><tr align="left"><td><span class="elsevierStyleSup">177</span>Lu</td><td>1&#46;3</td><td>0&#46;084</td><td>130</td><td>6&#46;7</td></tr><tr align="left"><td><span class="elsevierStyleSup">153</span>Sm</td><td>1&#46;6</td><td>0&#46;074</td><td>130</td><td>26&#46;1</td></tr></table><p class="elsevierStylePara">Both <span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span>Sm&#44; by their energetic properties&#44; can be used to treat small joints in advanced stages of arthritis&#46; On the other hand <span class="elsevierStyleSup">169</span>Er is used to treat small joints only<a href="&#35;bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">17</span></a>&#46;</p><p class="elsevierStylePara">The amount of radioactivity for a single intra-articular injection with <span class="elsevierStyleSup">169</span>Er depends on the joint size<a href="&#35;bib18" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a>&#58;</p><ul><li><p class="elsevierStylePara">10&#8211;20 MBq for proximal or distal interphalangeal joints&#44;</p></li><li><p class="elsevierStylePara">20&#8211;40 MBq for metacarpophalangeal or metatarsophalangeal joints&#44;</p></li><li><p class="elsevierStylePara">20&#8211;80 MBq for trapeziometacarpal joints&#46;</p></li></ul><p class="elsevierStylePara">Multiple joints may be treated simultaneously with a cumulative dose not exceeding 555MBq per patient</p><p class="elsevierStylePara">The absorbed dose estimated for a <span class="elsevierStyleSup">169</span>Er injected activity of 10 to 20MBq at a synovial depth of 0&#46;1mm is 910 to 1820Gy<a href="&#35;bib18" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a>&#46; This aspect should be taken into account to prescribe the activity in case of other radionuclides&#46;</p><p class="elsevierStylePara">In <a href="&#35;tbl7" class="elsevierStyleCrossRefs">tabla 7</a> are shown the activity values of <span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span>Sm to obtain the &#8220;<span class="elsevierStyleSup">169</span>Er dose equivalent&#8221; in the synovial membrane of small joints &#40;0&#46;1mm thickness of synovial lining cells and 13cm<span class="elsevierStyleSup">2</span> of synovium area&#41;&#46;</p><p class="elsevierStylePara">Table 7&#46; Values of activity administered of <span class="elsevierStyleSup">177</span>Lu and <span class="elsevierStyleSup">153</span>Sm to obtain the &#8220;<span class="elsevierStyleSup">169</span>Er dose equivalent&#8221; in the synovial membrane of an arthritics small joint &#40;0&#46;1mm thickness of synovial lining cells and 10cm<span class="elsevierStyleSup">2</span> of synovium area&#41;</p><a name="tbl7" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Radionuclide</td><td>X<span class="elsevierStyleInf">90</span></td><td><span class="elsevierStyleItalic">S</span>-value Gy&#47;h&#42;MBq</td><td>Absorbed dose &#40;Gy&#41;</td><td>Administered activity &#40;MBq&#41;</td></tr><tr align="left"><td><span class="elsevierStyleSup">169</span>Er</td><td>0&#46;2</td><td>0&#46;295</td><td>958</td><td>10</td></tr><tr align="left"><td><span class="elsevierStyleSup">177</span>Lu</td><td>1&#46;3</td><td>0&#46;335</td><td>958</td><td>12&#46;3</td></tr><tr align="left"><td><span class="elsevierStyleSup">153</span>Sm</td><td>1&#46;6</td><td>0&#46;294</td><td>958</td><td>48&#46;4</td></tr></table><p class="elsevierStylePara">This empirical approach to calculating the dose of a new radionuclide to be administered appears to provide basis to start new researches with different radionuclides&#46; However&#44; the nonexistence of theoretical sustentations for these calculations still make the clinical trials the only way to determine the dose of a new radionuclide that will be effective in a treatment&#46; Thus&#44; the clinical trials constitute the final bases to introduce new radionuclides for RSV&#46;</p><p class="elsevierStylePara">Curves displaying absorbed dose as a function of distance into the diseased synovium have been generated for each of the six beta-emitting radionuclides investigated &#40;<a href="&#35;fig1" class="elsevierStyleCrossRefs">figura 1</a>&#41;&#46; Having selected the appropriated radionuclide&#44; these curves can then be used by the clinician to predict the amount of activity required to deliver sufficient dose to a given synovial depth&#46;</p><a name="fig1" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="125v28n04-13140119fig1.jpg" alt="Absorbed doses profiles &#40;Gy&#42;cm&#60;sup&#62;2&#60;&#47;sup&#62;&#47;h&#42;MBq&#41; as a function of distance into the diseased synovium&#46;"></img></p><p class="elsevierStylePara">Fig&#46; 1&#46; Absorbed doses profiles &#40;Gy&#42;cm<span class="elsevierStyleSup">2</span>&#47;h&#42;MBq&#41; as a function of distance into the diseased synovium&#46;</p><span class="elsevierStyleSectionTitle">Articular cartilage</span><p class="elsevierStylePara">The presence of the healthy articular cartilage in the arthritic joint limits the prescribed treatment activity&#46; The question of harmful effect of &#946; radiation in the articular cartilage has always been a subject of debate&#46; According to Johnson et al<a href="&#35;bib9" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a>&#44; for a cartilage thickness of 2mm&#46; a dose of 1Gy is reached at a depth of 1&#46;5mm in the adjoining bone with 185MBq of <span class="elsevierStyleSup">90</span>Y&#46; Thus&#44; the &#946; radiation induces no systemic effect&#46; Absorbed doses profiles in the articular cartilage versus distance are presented in <a href="&#35;fig2" class="elsevierStyleCrossRefs">figura 2</a>&#46;</p><a name="fig2" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="125v28n04-13140119fig2.jpg" alt="Absorbed doses profiles &#40;Gy&#42;cm&#60;sup&#62;2&#60;&#47;sup&#62;&#47;h&#42;MBq&#41; as a function of distance into the articular cartilage&#46;"></img></p><p class="elsevierStylePara">Fig&#46; 2&#46; Absorbed doses profiles &#40;Gy&#42;cm<span class="elsevierStyleSup">2</span>&#47;h&#42;MBq&#41; as a function of distance into the articular cartilage&#46;</p><p class="elsevierStylePara">Results presented in this paper are in agreement whit those found in the references <a href="&#35;bib9" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib10" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib11" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib17" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib18" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a>&#46;</p><span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStylePara">In RSV&#44; the radionuclide choice is critical since the synovial thickness of different joints in the human body &#40;e&#46;g&#46;&#44; finger&#44; wrist&#44; knee&#44; etc&#46;&#41; vary substantially&#46; Also&#44; joints at different stages of the disease show different degrees of swelling and may also call for a beta emitter of different penetration&#46; Each patient should have a MRI study prior to RSV in order to determine the tissue volume and to select the appropriated dose and radionuclides to be used&#44; eliminating the practice of fixed radionuclides and doses for the treatment of different kind of joints&#44; methodology applied in many clinics in Europe<a href="&#35;bib19" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a href="&#35;bib20" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">20</span></a>&#46; The selection of the radionuclide for the treatment will depend on the thickness of the synovium to be treated and the proximity of the non target organs to the joint &#40;bone and articular cartilage&#41;&#46; Values here presented can be a useful tool to prescribe adequate quantities of new radionuclides for RSV&#46; Additionally&#44; provide information about the radiation damage to articular cartilage&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">El principal objetivo de este trabajo fue obtener los perfiles de dosis para los radion&#250;clidos de uso frecuente en radiosinoviortesis&#46; Estos perfiles revelan la dosis absorbida impartida por unidad de actividad del radion&#250;clido inyectado &#40;Gy&#47;h&#42;MBq&#41; en la membrana sinovial y el cart&#237;lago articular&#46; Los radion&#250;clidos seleccionados fueron <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm and <span class="elsevierStyleSup">169</span>Er&#46; Tambi&#233;n fue calculado el rango terap&#233;utico de cada radion&#250;clido en el tejido sinovial&#46; Este rango determina el grosor synovial que puede ser irradiado suficientemente y por lo tanto&#44; tratado con &#233;xito&#46; Los valores S para la membrana sinovial y el cart&#237;lago articular fueron calculados usando como modelo un cilindro con la fuente distribuida uniformemente en su volumen&#46; La membrana sinovial fue simulada variando el radio del cilindro &#40;rango 0&#46;5cm&#8211;9cm&#41; y su altura &#40;rango 0&#46;01cm&#8211;0&#46;04cm&#41;&#46; La variaci&#243;n del radio del cilindro representa varios tama&#241;os de superficie sinovial &#40;articulaciones peque&#241;as&#44; medianas y grandes&#41;&#44; y se define como el &#225;rea de la base del cilindro&#59; la variaci&#243;n de la altura&#44; representa diferentes estados de progresi&#243;n de la artritis reumatoide&#46; El mismo modelo fue empleado para la simulaci&#243;n del cart&#237;lago articular&#44; pero la fuente fue uniformemente distribuida dentro de una capa cil&#237;ndrica &#40;0&#46;01cm&#41; y 1cm de radio&#46; Los resultados obtenidos permiten la estimaci&#243;n de la dosis que ser&#225; entregada a la membrana sinovial y el cart&#237;lago articular para diferentes tama&#241;os de articulaci&#243;n y diferentes estados de progresi&#243;n de la artritis reum&#225;tica&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses&#46; These profiles reveal the absorbed dose per activity of injected radionuclide &#40;Gy&#47;h&#42;MBq&#41; in the synovial membrane and the articular cartilage&#46; The researched radionuclides were <span class="elsevierStyleSup">32</span>P&#44; <span class="elsevierStyleSup">90</span>Y&#44; <span class="elsevierStyleSup">188</span>Re&#44; <span class="elsevierStyleSup">177</span>Lu&#44; <span class="elsevierStyleSup">153</span>Sm and <span class="elsevierStyleSup">169</span>Er&#46; The therapeutic range of each radionuclides in synovial tissue were also calculated&#46; This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated&#46; The S values for the synovial membrane and articular cartilage were calculated using as a model a cylinder with the source uniformly distributed in its volume&#46; The synovial membrane was simulated varying the radius of the cylinder &#40;from 0&#46;5cm to 9cm&#41; and its height &#40;from 0&#46;01cm to 0&#46;04cm&#41;&#46; The area in the base of the cylinder represents different sizes of the synovial surface &#40;small&#44; medium and large joints&#41;&#46; The height of the cylinder represents different stages of the progression of the rheumatoid arthritis&#46; The same model was used to simulate the articular cartilage but&#44; the source was uniformly distributed into a cylindrical slab &#40;0&#46;01cm height and 1cm of radius&#46; The results obtained allow the estimation of the dose that will be delivered to the synovial membrane and the articular cartilage for different joint sizes and different stages of progression of the rheumatoid arthritis &#40;RA&#41;&#46;</p>"
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Article information

ISSN: 2253654X
Original language: English

DOI:10.1016/S0212-6982(09)00006-8

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	0	8	8
2024 September	0	11	11
2024 August	0	4	4
2024 July	0	6	6
2024 June	6	6	12
2024 May	0	10	10
2024 April	0	5	5
2024 March	0	5	5
2024 February	0	3	3
2024 January	0	5	5
2023 December	0	5	5
2023 November	0	3	3
2023 October	5	8	13
2023 September	0	1	1
2023 August	0	6	6
2023 July	0	10	10
2023 May	0	5	5
2023 April	0	5	5
2023 March	2	6	8
2023 February	0	6	6
2023 January	0	6	6
2022 December	0	2	2
2022 November	0	8	8
2022 October	0	9	9
2022 September	0	7	7
2022 August	0	2	2
2022 July	0	7	7
2022 June	0	3	3
2022 May	0	3	3
2022 April	0	4	4
2022 March	0	8	8
2022 January	0	1	1
2021 December	0	5	5
2021 November	0	3	3
2021 October	0	9	9
2021 September	1	10	11
2021 August	0	9	9
2021 July	0	4	4
2021 June	0	5	5
2021 May	0	6	6
2021 April	0	30	30
2021 March	0	5	5
2021 February	0	3	3
2021 January	0	6	6
2020 December	0	7	7
2020 November	0	9	9
2020 October	0	4	4
2020 September	0	17	17
2020 August	0	14	14
2020 June	0	6	6
2020 May	0	4	4
2020 April	0	6	6
2020 March	0	4	4
2020 February	0	1	1
2020 January	0	3	3
2019 December	0	6	6
2019 November	0	10	10
2019 October	0	8	8
2019 September	0	6	6
2019 August	0	1	1
2019 July	0	4	4
2019 June	0	5	5
2019 May	0	19	19
2019 April	0	8	8
2019 February	0	2	2
2018 December	0	1	1
2018 October	0	3	3
2018 February	11	0	11
2018 January	5	0	5
2017 December	10	1	11
2017 November	13	3	16
2017 October	15	5	20
2017 September	14	4	18
2017 August	24	3	27
2017 July	6	2	8
2017 June	12	18	30
2017 May	23	3	26
2017 April	26	3	29
2017 March	28	15	43
2017 February	9	3	12
2017 January	9	2	11
2016 December	15	7	22
2016 November	25	3	28
2016 October	48	11	59
2016 September	20	5	25
2016 August	25	6	31
2016 July	18	1	19
2016 June	18	7	25
2016 May	15	15	30
2016 April	6	7	13
2016 March	10	19	29
2016 February	11	18	29
2016 January	11	11	22
2015 December	12	10	22
2015 November	19	19	38
2015 October	28	21	49
2015 September	23	11	34
2015 August	26	8	34
2015 July	22	6	28
2015 June	10	4	14
2015 May	8	7	15
2015 April	18	18	36
2015 March	12	12	24
2015 February	8	5	13
2015 January	23	9	32
2014 December	17	4	21
2014 November	6	0	6
2014 October	11	1	12
2014 September	8	0	8
2014 August	10	1	11
2014 July	12	4	16
2014 June	13	1	14
2014 May	7	0	7
2014 April	12	4	16
2014 March	6	4	10
2014 February	6	1	7
2014 January	7	1	8
2013 December	9	2	11
2013 November	9	4	13
2013 October	12	3	15
2013 September	14	1	15
2013 August	16	2	18
2013 July	7	1	8
2013 June	1	0	1
2013 May	4	0	4
2009 June	719	0	719

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