array:23 [ "pii" => "S2253808913001304" "issn" => "22538089" "doi" => "10.1016/j.remnie.2013.09.013" "estado" => "S300" "fechaPublicacion" => "2013-11-01" "aid" => "522" "copyright" => "Elsevier España, S.L. and SEMNIM" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Rev Esp Med Nucl Imagen Mol. 2013;32:371-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 758 "formatos" => array:2 [ "HTML" => 532 "PDF" => 226 ] ] "itemSiguiente" => array:19 [ "pii" => "S2253808913001225" "issn" => "22538089" "doi" => "10.1016/j.remnie.2013.09.005" "estado" => "S300" "fechaPublicacion" => "2013-11-01" "aid" => "523" "copyright" => "Elsevier España, S.L. and SEMNIM" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Rev Esp Med Nucl Imagen Mol. 2013;32:378-86" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2934 "formatos" => array:2 [ "HTML" => 2538 "PDF" => 396 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Continuing education</span>" "titulo" => "Update on the use of PET radiopharmaceuticals in inflammatory disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "378" "paginaFinal" => "386" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización del uso de radiotrazadores PET en patología inflamatoria" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 872 "Ancho" => 1400 "Tamanyo" => 175950 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A 39-year-old male with an acute episode of Crohn's disease. In the <span class="elsevierStyleSup">18</span>F-FDG PET/CT (A: maximum intensity projection image, B: coronal slices and C: axial slices) an increased <span class="elsevierStyleSup">18</span>F-FDG uptake was observed in the wall of the ascending colon (demonstrating areas of dilatation and thickening and other zones of stenosis), transverse colon and a large part of the descending colon, the distal portion of which also presented dilatation. The involvement demonstrated by PET/CT was more extense than that determined by endoscopy.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Martínez-Rodríguez, J.M. Carril" "autores" => array:2 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Martínez-Rodríguez" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Carril" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X13001212" "doi" => "10.1016/j.remn.2013.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X13001212?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808913001225?idApp=UINPBA00004N" "url" => "/22538089/0000003200000006/v1_201311020040/S2253808913001225/v1_201311020040/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2253808913001389" "issn" => "22538089" "doi" => "10.1016/j.remnie.2013.10.001" "estado" => "S300" "fechaPublicacion" => "2013-11-01" "aid" => "132" "copyright" => "Elsevier España, S.L. and SEMNIM" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Rev Esp Med Nucl Imagen Mol. 2013;32:364-70" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 722 "formatos" => array:2 [ "HTML" => 531 "PDF" => 191 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Clinical validation of the planar radionuclide ventriculography in patients with right ventricular dysfunction" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "364" "paginaFinal" => "370" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Validación clínica de la ventriculografía isotópica planar en pacientes con disfunción del ventrículo derecho" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3433 "Ancho" => 3129 "Tamanyo" => 818205 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Summary of blood pool gated pictures, amplitude and phase images, LV and RV phase histograms and values of functional variables in one case of ARVD.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Bontemps, Y. Merabet, P. Chevalier, R. Itti" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Bontemps" ] 1 => array:2 [ "nombre" => "Y." "apellidos" => "Merabet" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Chevalier" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Itti" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2253654X13000577" "doi" => "10.1016/j.remn.2013.04.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X13000577?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808913001389?idApp=UINPBA00004N" "url" => "/22538089/0000003200000006/v1_201311020040/S2253808913001389/v1_201311020040/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Dynamic behaviour of selected PET tracers in embryonated chicken eggs" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "371" "paginaFinal" => "377" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P. Gebhardt, L. Würbach, A. Heidrich, L. Heinrich, M. Walther, T. Opfermann, B. Sørensen, H.P. Saluz" "autores" => array:8 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Gebhardt" "email" => array:2 [ 0 => "peter.gebhardt@hki-jena.de" 1 => "peter.gebhardt@yahoo.de" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Würbach" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Heidrich" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "L." "apellidos" => "Heinrich" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Walther" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "T." "apellidos" => "Opfermann" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "B." "apellidos" => "Sørensen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "H.P." "apellidos" => "Saluz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knöll-Institute, Jena, Germany" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Friedrich Schiller University of Jena, Jena, Germany" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding authors." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Comportamiento dinámico de marcadores PET seleccionados en huevos de gallina embrionados" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 511 "Ancho" => 1123 "Tamanyo" => 45317 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Structure of the <span class="elsevierStyleSup">18</span>F-sulphonamide (<span class="elsevierStyleBold">1</span>).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In basic research, molecular imaging methods are a means of studying biological processes in living systems. PET/CT combines two modalities. In positron emission tomography (PET), the distribution of a tracer compound carrying a positron-emitting isotope can be followed because it interacts with potential target sites. Thereby, regions of interest (ROIs) deep in the body can also be observed and quantified because the 511<span class="elsevierStyleHsp" style=""></span>keV gamma ray photons can easily penetrate organic material. Computed tomography (CT) provides the anatomical information necessary to specify the point of tracer uptake. The resolution of microPET is in the range of 1.5<span class="elsevierStyleHsp" style=""></span>mm, and that of CT can reach 50<span class="elsevierStyleHsp" style=""></span>μm.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The chick embryo is a well-established model organism in infection biology,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–5</span></a> oncology,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–8</span></a> and pharmacology.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Avian embryogenesis has been extensively studied by in vivo imaging methods.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However, only recently has microPET/CT been implemented to investigate metabolic processes in the chick embryo.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Innovative anaesthetic<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and tracer-injection techniques have resolved the problems encountered during the molecular imaging of chick embryos via microPET/CT.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Following the success of experiments in which [<span class="elsevierStyleSup">18</span>F]fluoride was injected,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> we investigated biologically active isotopes and molecules in the in vivo chick embryo. These included 2-deoxy-2-[<span class="elsevierStyleSup">18</span>F]fluoroglucose ([<span class="elsevierStyleSup">18</span>F]FDG), a glucose analogue that accumulates in regions of enhanced metabolism, <span class="elsevierStyleSup">68</span>Ga citrate, which can help diagnose bone infection,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> a <span class="elsevierStyleSup">68</span>Ga-labelled albumin desferrioxamine conjugate as a blood pool marker,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and a <span class="elsevierStyleSup">68</span>Ga-labelled amyloid-fibril-binding antibody (<span class="elsevierStyleSup">68</span>Ga-B10).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> We also took advantage of the chick embryo model to investigate the properties of a recently synthesised sulphonamide, N-(4-[<span class="elsevierStyleSup">18</span>F]fluoro-6-methylpyrimidin-2-yl)-4-nitrobenzenesulphonamide (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), which was developed as an experimental precursor compound.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Although these tracers were designed for application in mammals, we demonstrate that microPET/CT can be successfully utilised to investigate the general distribution and accumulation patterns in healthy chick embryos, thereby increasing the usefulness of this model organism.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035"><span class="elsevierStyleSup">18</span>F-labelled compounds</span><p id="par0025" class="elsevierStylePara elsevierViewall">The [<span class="elsevierStyleSup">18</span>F]FDG was from Eckert & Ziegler, f-con Deutschland GmbH (Holzhausen, Germany).</p><p id="par0030" class="elsevierStylePara elsevierViewall">N-(4-[<span class="elsevierStyleSup">18</span>F]fluoro-6-methylpyrimidin-2-yl)-4-nitrobenzenesulphonamide was synthesised as described.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040"><span class="elsevierStyleSup">68</span>Ga-labelled compounds</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Preparation of desferrioxamine conjugates</span><p id="par0035" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate was synthesised as described<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> with some modifications. Before derivatisation of the albumin, 5<span class="elsevierStyleHsp" style=""></span>ml of 0.68% BSA (Carl Roth, Karlsruhe, Germany) in Ca<span class="elsevierStyleSup">2+</span>- and Mg<span class="elsevierStyleSup">2+</span>-free Dulbecco's PBS (PAA Laboratories GmbH, Pasching, Austria) were concentrated twofold using Microsep 3K Centrifugal Devices (Pall, Dreieich, Germany, MCP003C41). The albumin solution was then washed once with 2<span class="elsevierStyleHsp" style=""></span>ml of 86<span class="elsevierStyleHsp" style=""></span>mM EDTA and four times with PBS. The volume was then adjusted to 5<span class="elsevierStyleHsp" style=""></span>ml with PBS. To 0.5<span class="elsevierStyleHsp" style=""></span>ml of the solution were added 6<span class="elsevierStyleHsp" style=""></span>μl of desferrioxamine-p-SCN (0.07<span class="elsevierStyleHsp" style=""></span>mg in DMSO, 2.4 fold excess, Macrocyclics, Dallas/TX, USA). The pH was adjusted to 9.0 with 0.1<span class="elsevierStyleHsp" style=""></span>M sodium carbonate, and the reaction was carried out at 37<span class="elsevierStyleHsp" style=""></span>°<span class="elsevierStyleSmallCaps">C</span> over 45<span class="elsevierStyleHsp" style=""></span>min. The conjugate was then purified by size exclusion chromatography (PD-25, GE Healthcare Europe GmbH) with 0.25<span class="elsevierStyleHsp" style=""></span>M sodium acetate (pH 5.5) as the eluent. The flow through and an additional 250<span class="elsevierStyleHsp" style=""></span>μl of eluate were discarded. The next 700<span class="elsevierStyleHsp" style=""></span>μl was collected and stored at 4<span class="elsevierStyleHsp" style=""></span>°C. Further purification was performed with 3<span class="elsevierStyleHsp" style=""></span>K centrifugal filters (Amicon Ultra-0.5<span class="elsevierStyleHsp" style=""></span>ml, Merck Millipore, Schwalbach, Germany). For this, 500<span class="elsevierStyleHsp" style=""></span>μl of the albumin desferrioxamine conjugate were concentrated fivefold and washed five times with 400<span class="elsevierStyleHsp" style=""></span>μl of 0.25<span class="elsevierStyleHsp" style=""></span>M ammonium acetate. After removal from the filter unit, the volume was adjusted to 0.5<span class="elsevierStyleHsp" style=""></span>ml.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The desferrioxamine conjugate of the amyloid fibril-binding antibody (B10)<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> was synthesised as described for the albumin. It was diluted in PBS to give a concentration of 5<span class="elsevierStyleHsp" style=""></span>mg/ml. After size exclusion chromatography, the conjugate was labelled without further purification.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Labelling of proteins</span><p id="par0045" class="elsevierStylePara elsevierViewall">[<span class="elsevierStyleSup">68</span>Ga]Gallium chloride was eluted from a <span class="elsevierStyleSup">68</span>Ge/<span class="elsevierStyleSup">68</span>Ga generator (iThemba LABS, Somerset West, South Africa). The eluate was concentrated as described,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> mixed with 100<span class="elsevierStyleHsp" style=""></span>μl of 1.1<span class="elsevierStyleHsp" style=""></span>M sodium acetate, and the pH was adjusted stepwise to 4.7–5.0 with 2.0<span class="elsevierStyleHsp" style=""></span>M sodium carbonate. A volume of 200<span class="elsevierStyleHsp" style=""></span>μl of the albumin desferrioxamine conjugate or B10 desferrioxamine conjugate was added to the eluate, followed by incubation for 5<span class="elsevierStyleHsp" style=""></span>min.</p><p id="par0050" class="elsevierStylePara elsevierViewall">As quality control, instant thin layer chromatography (ITLC) was performed on dark green tec-control strips (Elimpex-Medizintechnik GesmbH, Mödling, Austria) using 20<span class="elsevierStyleHsp" style=""></span>mM citric acid (pH 4.9) as the eluent. The labelled proteins were found at the origin, while free <span class="elsevierStyleSup">68</span>Ga<span class="elsevierStyleSup">3+</span> ran with the solvent front. Additionally, radio HPLC was performed with a C-4 reverse phase column (Jupiter 5u, 300<span class="elsevierStyleHsp" style=""></span>A, 150<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4.6<span class="elsevierStyleHsp" style=""></span>mm, Phenomenex, Aschaffenburg, Germany) and a gradient system which started from 80% buffer A with 20% buffer B coming to 5% buffer A with 95% buffer B over 20<span class="elsevierStyleHsp" style=""></span>min changing then to 5<span class="elsevierStyleHsp" style=""></span>min of initial conditions. Buffer A was 95% water/5% ACN/0.05% TFA (v/v/v) and buffer B was 75% ACN/20% 2-propanol/4.1% water/0.85% TFA (v/v/v/v). Free <span class="elsevierStyleSup">68</span>Ga salt was detected at 2–3<span class="elsevierStyleHsp" style=""></span>min, and the labelled tracer was detected at approximately 10<span class="elsevierStyleHsp" style=""></span>min. The labelling efficiency was between 90 and 97%.</p><p id="par0055" class="elsevierStylePara elsevierViewall">For <span class="elsevierStyleSup">68</span>Ga citrate, 50<span class="elsevierStyleHsp" style=""></span>μl of 0.01<span class="elsevierStyleHsp" style=""></span>M citric acid was added to 150<span class="elsevierStyleHsp" style=""></span>μl of the <span class="elsevierStyleSup">68</span>GaCl<span class="elsevierStyleInf">3</span> eluate, and the pH was adjusted to 6.0 with 2.0<span class="elsevierStyleHsp" style=""></span>M sodium carbonate. Quality control was performed using ITLC as described above. The pH of the tracer solution was adjusted to 6.2–6.5 prior to injection.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ligand free <span class="elsevierStyleSup">64</span>Cu</span><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">64</span>Cu chloride was produced as described by Thieme et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Preparation of embryonated chicken eggs, catheter system and tracer injection</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Gallus gallus domesticus</span> eggs were prepared as it is fully described by Würbach et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Briefly, for dynamic experiments, 15–18 day old embryos were catheterised via the chorioallantoic membrane (CAM). For this the custom-made catheter of 22<span class="elsevierStyleHsp" style=""></span>cm in length with a 30<span class="elsevierStyleHsp" style=""></span>G needle was inserted through an opening of about 1<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span> into an blood vessel of sufficient size on the CAM and closed with a stopper. The integrity of the system was checked (leakage of blood), and the opening was closed with paraffin wax, also fastening the catheter.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Injection of tracers was made after the CT measurement. Approximately 5<span class="elsevierStyleHsp" style=""></span>s before tracer injection, the PET scan was started. Tracers (150<span class="elsevierStyleHsp" style=""></span>μl, diluted in PBS) were injected over 40–60<span class="elsevierStyleHsp" style=""></span>s.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Anaesthesia and assembly during measurement</span><p id="par0075" class="elsevierStylePara elsevierViewall">The embryos were anaesthetised as described<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> during the full time of measurement. Briefly, the embryos were kept under red light and with an oxygen flow of 3<span class="elsevierStyleHsp" style=""></span>l/min (5% isoflurane) for 15<span class="elsevierStyleHsp" style=""></span>min in a commercially available anaesthesia induction chamber (inner dimensions: 180<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>260<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>140<span class="elsevierStyleHsp" style=""></span>mm, Rothacher Medical GmbH, Switzerland) anaesthesia was induced. For microPET/CT measurement the embryos were then placed in a 14<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>cm plastic bag and fixed with transparent tape. The reclosable bag was supplied via a 8<span class="elsevierStyleHsp" style=""></span>mm silicone tube with 1.5<span class="elsevierStyleHsp" style=""></span>l/min O<span class="elsevierStyleInf">2</span> (1.5% isoflurane) from a veterinary anaesthesia system (combi-vet<span class="elsevierStyleSup">®</span> base system; Rothacher Medical GmbH, Switzerland). The catheters were fixed in place with tape, which could easily be removed for PET measurements.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Imaging system and imaging protocols</span><p id="par0080" class="elsevierStylePara elsevierViewall">For imaging a Siemens Inveon Small Animal microPET/CT scanner (Siemens Medical Solutions, Siemens Healthcare Molecular Imaging, USA) was used. PET data were acquired for 1<span class="elsevierStyleHsp" style=""></span>h, 4<span class="elsevierStyleHsp" style=""></span>h, and overnight (14.75<span class="elsevierStyleHsp" style=""></span>h). Investigations over 1<span class="elsevierStyleHsp" style=""></span>h were performed at least in triplicate, the 4<span class="elsevierStyleHsp" style=""></span>h experiments were performed at least in duplicate, and a single sample was used for the 14.75<span class="elsevierStyleHsp" style=""></span>h experiment.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The dynamic microPET data acquired from the 1<span class="elsevierStyleHsp" style=""></span>h measurements were divided into 51 time frames (15<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>25, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>75, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>125, and 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>s). The data from the 4<span class="elsevierStyleHsp" style=""></span>h measurements were divided into 75 time frames (15<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>25, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>75, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>125, 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>200, 12<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>300, and 12<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>600). For the overnight experiment (14.75<span class="elsevierStyleHsp" style=""></span>h) with <span class="elsevierStyleSup">64</span>Cu chloride, we used 104 time frames (15<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10, 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>25, 9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>75, 5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>125, 4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>250, 4<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>400, 1<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>500, 3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>800 and 51<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>900).</p><p id="par0090" class="elsevierStylePara elsevierViewall">The images were histogrammed and reconstructed with Inveon Acquisition Software (IAW, version 1.5.0.28; Siemens Medical Solutions, Siemens Healthcare Molecular Imaging, USA). In short, 3D ordered-subset expectation maximisation (OSEM3D) was used, followed by maximum <span class="elsevierStyleItalic">a posteriori</span> (MAP) reconstruction with image zoom<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1, image size<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>256 and a requested resolution of 1.635 (<span class="elsevierStyleItalic">β</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.1) resulting in voxel sizes of 0.388<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>0.388<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>0.796<span class="elsevierStyleHsp" style=""></span>mm.</p><p id="par0095" class="elsevierStylePara elsevierViewall">For attenuation correction of microPET data, microCT scans were performed (<span class="elsevierStyleSmallCaps">X</span>-ray tube voltage: 80<span class="elsevierStyleHsp" style=""></span>kV, <span class="elsevierStyleSmallCaps">X</span>-ray tube current: 500<span class="elsevierStyleHsp" style=""></span>μA) at two animal bed positions. The <span class="elsevierStyleSmallCaps">X</span>-ray detector was operated in a four-by-four pixel binning mode and 201 projections were acquired per bed position over a 360° rotation of the gantry. The total <span class="elsevierStyleSmallCaps">X</span>-ray exposure time was 120.6<span class="elsevierStyleHsp" style=""></span>s.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Image analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Images were analysed with Inveon Research Workplace software (IRW, version 3.0, Siemens Medical Solutions, Siemens Healthcare Molecular Imaging, USA). This software allowed for automated decay correction in dependence of the applied isotope. Some of the tracer remained in the catheter system. To correct this we calculated a total injected activity (TID<span class="elsevierStyleInf">egg</span>). The TID<span class="elsevierStyleInf">egg</span> was determined by drawing a ROI over the whole egg excluding the catheter. The mean activity concentration of the ROI<span class="elsevierStyleInf">egg</span> was then multiplied by the egg volume giving the TID<span class="elsevierStyleInf">egg</span>. The corrected injected dose of ROIs (%ID<span class="elsevierStyleInf">corr</span>/g), was calculated from the mean activity concentration (CROI) which was divided by the TID<span class="elsevierStyleInf">egg</span> and multiplied by 100%.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Anatomic localisation of targets was guided by rotating PET-MIPs in combination with the CT slices. By this way mapping of ROIs were either possible by assigning of typical shapes of PET-signals (e.g. U-shape of heart in the first 2<span class="elsevierStyleHsp" style=""></span>min) or typical bone structures (e.g. the hemicycle of the skull). The acquired images were used to quantify tracer uptake in the heart, liver, left joint, left tarsometatarsus, and brain as representative ROIs. The ROIs were drawn as ellipsoids and manually edited to avoid overlap (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A–D). A threshold of 40% was used to explore the appropriate shape of the ROIs. The bone regions were drawn with a 10% threshold in the CT modality (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>E). To find the heart region, the first frames (30–60<span class="elsevierStyleHsp" style=""></span>s) were combined. The blood content of tracers was not determined. Only the U-shaped heart was focussed on in order to avoid adding latter frames that involve influx of the tracer into the liver. The other sites of uptake were drawn in the time frames of 30–60<span class="elsevierStyleHsp" style=""></span>min after injection. If no tracer was absorbed, ROIs of appropriate volumes were drawn according to the CT image. For correction means in terms of the partial volume effect, a recovery coefficient of 0.713 was used for the tarsometatarsus.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The other ROIs were out of the range of necessary corrections.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results and discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">Embryonated chicken eggs of day 15–18 are in a late stage of growth. Although the organs are developed and the immune system is operational growth is still incomplete,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Glucose metabolism<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and other metabolic activities can be observed. As part of the renal system, the metanephric kidneys are fully functional by day 15 of incubation. The development of the renal system in chicken embryos and mammals is similar except that birds retain the cloaca (and do not form a bladder). We investigated the distribution of several conventional ([<span class="elsevierStyleSup">18</span>F]FDG, <span class="elsevierStyleSup">68</span>Ga citrate and <span class="elsevierStyleSup">68</span>Ga-albumin) and recently developed (<span class="elsevierStyleSup">68</span>Ga-B10, <span class="elsevierStyleSup">18</span>F-sulphonamide and <span class="elsevierStyleSup">64</span>Cu chloride) PET tracers in the organs of chicken embryos over different time spans. These tracers were either selected because they are commonly used for standard PET measurements or because they are a focus of our current research. In initial experiments, the 4D microPET/CT measurements were recorded over 1<span class="elsevierStyleHsp" style=""></span>h covering the usual PET operating times to identify the uptake in the heart, liver, joints and bones. To confirm the initial trends, images were acquired with a more restricted number of individuals over longer time periods. The <span class="elsevierStyleSup">68</span>Ga and <span class="elsevierStyleSup">18</span>F-tracers were observed over 4<span class="elsevierStyleHsp" style=""></span>h, while ligand-free <span class="elsevierStyleSup">64</span>Cu chloride was measured overnight.</p><p id="par0115" class="elsevierStylePara elsevierViewall">To illustrate the similarities and differences between the compounds, the maximum intensity projections (MIPs) were applied. Summing the early time frames between 0 and 30<span class="elsevierStyleHsp" style=""></span>s, we see the U-shape of the heart region for all tracers (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The [<span class="elsevierStyleSup">18</span>F]FDG flowed through the heart and then accumulated in the liver (4–6<span class="elsevierStyleHsp" style=""></span>min) and growth zones of the bones (20–60<span class="elsevierStyleHsp" style=""></span>min) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>a, 1st line). To enhance the tips of bones as target sites after [<span class="elsevierStyleSup">18</span>F]FDG injection, we applied [<span class="elsevierStyleSup">18</span>F]Fluoride (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>a, 2nd line) and measured an additional hour. Both tracers clearly complement each other at the target sites. After 4–6<span class="elsevierStyleHsp" style=""></span>min, signals in the middle of the bones arise and diffuse through the entire skeleton after 1<span class="elsevierStyleHsp" style=""></span>h. Thereby, the [<span class="elsevierStyleSup">18</span>F]FDG activity remained as green signals at the growth zones of bones. <span class="elsevierStyleSup">68</span>Ga citrate rapidly accumulated in the liver (1–2<span class="elsevierStyleHsp" style=""></span>min), but after 4<span class="elsevierStyleHsp" style=""></span>h, the activity was equally distributed (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>b). The <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate was also rapidly absorbed by the liver, but over 4<span class="elsevierStyleHsp" style=""></span>h, some activity was found in the entire embryo (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>c), while the activity of <span class="elsevierStyleSup">68</span>Ga-B10 only increased in the liver (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>d). Copper-64, injected as <span class="elsevierStyleSup">64</span>CuCl<span class="elsevierStyleInf">2</span>-solution, was initially observed in the bloodpool (0–20<span class="elsevierStyleHsp" style=""></span>min) but later accumulated in the liver (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>e). After 20<span class="elsevierStyleHsp" style=""></span>min, activity was observed in the liver, and after 14.75<span class="elsevierStyleHsp" style=""></span>h, the signal remained exclusively in the liver. The <span class="elsevierStyleSup">18</span>F-sulphonamide tracer was absorbed by the liver (1–2<span class="elsevierStyleHsp" style=""></span>min), followed by a strong signal in kidneys (4–6<span class="elsevierStyleHsp" style=""></span>min) and accumulation in bones (20–60<span class="elsevierStyleHsp" style=""></span>min, <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>f).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Properties of tracers observed in experiments with chicken eggs</span><p id="par0120" class="elsevierStylePara elsevierViewall">The behaviour of the tracers can be summarised as follows:</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">[<span class="elsevierStyleSup">18</span>F]FDG</span><p id="par0125" class="elsevierStylePara elsevierViewall">Because of high metabolism, [<span class="elsevierStyleSup">18</span>F]FDG rapidly accumulates in areas of bone growth. Within 4–6<span class="elsevierStyleHsp" style=""></span>min of injection (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>), activity increased at the bone ends (joints) and in the spine. After 4<span class="elsevierStyleHsp" style=""></span>h, the tracer was cleared from other targets.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095"><span class="elsevierStyleSup">68</span>Ga citrate and <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate</span><p id="par0130" class="elsevierStylePara elsevierViewall">In all targets except for the brain, the <span class="elsevierStyleSup">68</span>Ga citrate and <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate curves approached a plateau by 4<span class="elsevierStyleHsp" style=""></span>h. In the heart and liver, uptake values of the <span class="elsevierStyleSup">68</span>Ga citrate were less than those of the <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate. At later time points, <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate values for the liver exceeded those of the heart. The values of the citrate tracer in the joint and tarsometatarsus were similar to <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate after 4<span class="elsevierStyleHsp" style=""></span>h.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100"><span class="elsevierStyleSup">64</span>Cu chloride</span><p id="par0135" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleSup">64</span>Cu chloride was mainly taken up by the liver, while the activity absorbed was maintained by the other organs during the first hour as comparable high background level. After 14.75<span class="elsevierStyleHsp" style=""></span>h, the uptake value in the liver was 24.54% ID/g. This finding points to a fundamental difference between in vivo chick embryo studies and other animal studies (e.g. mice and rat); the main part of the tracer is excreted from the body during the first minutes or hours.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105"><span class="elsevierStyleSup">68</span>Ga-labelled amyloid-fibril-binding antibody (<span class="elsevierStyleSup">68</span>Ga-B10)</span><p id="par0140" class="elsevierStylePara elsevierViewall">This tracer readily accumulated in the liver and moderately in the heart but was only slightly absorbed by the other targets. The curve has the shape of a typical time activity curve (TAC) of accumulation. Because of the distinct shape compared with the other investigated tracers, <span class="elsevierStyleSup">68</span>Ga-B10 is presumably trapped in the liver.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">N-(4-[<span class="elsevierStyleSup">18</span>F]fluoro-6-methylpyrimidin-2-yl)-4-nitrobenzenesulphonamide</span><p id="par0145" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleSup">18</span>F-sulphonamide was rapidly taken up by the liver (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>, 1–2<span class="elsevierStyleHsp" style=""></span>min) and excreted in the kidneys (20<span class="elsevierStyleHsp" style=""></span>min) and bones (20<span class="elsevierStyleHsp" style=""></span>min, 1<span class="elsevierStyleHsp" style=""></span>h). This tracer was absorbed differently than [<span class="elsevierStyleSup">18</span>F]FDG, suggesting that metabolic processes had cleaved <span class="elsevierStyleSup">18</span>F from the heterocyclic ring. The dynamic behaviour of [<span class="elsevierStyleSup">18</span>F]fluoride in embryonated chicken eggs was recently described (as bone seeking agent).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The similar activity accumulation of <span class="elsevierStyleSup">18</span>F-sulphonamide in bones therefore seems to be evident for this proposed route fluoride cleavage.</p></span></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0150" class="elsevierStylePara elsevierViewall">We successfully used microPET/CT to examine the distribution of several tracers in the in vivo chick embryo model. [<span class="elsevierStyleSup">18</span>F]FDG was absorbed in the growth zones of bones because of the high metabolism at this side due to their need of a strong skeleton as precocial birds. This is similar to common rodent models, in which [<span class="elsevierStyleSup">18</span>F]FDG accumulates in regions of enhanced metabolism. <span class="elsevierStyleSup">68</span>Ga citrate remained in the blood pool. In comparison, more activity of the <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate was found in the liver after 4<span class="elsevierStyleHsp" style=""></span>h. The <span class="elsevierStyleSup">68</span>Ga-labelled amyloid-fibril-binding antibody (<span class="elsevierStyleSup">68</span>Ga-B10) increased in the liver, as it is normally observed at antibodies. <span class="elsevierStyleSup">64</span>Cu chloride also targets the liver (but more slowly), which is probably a result of the incorporation in enzymes such as super oxide dismutase. With respect to the <span class="elsevierStyleSup">18</span>F-sulphonamide, we would hypothesise that the C<span class="elsevierStyleGlyphsbnd"></span><span class="elsevierStyleSup">18</span>F bond on the heterocyclic ring system was rapidly cleaved in the liver, resulting in the release of [<span class="elsevierStyleSup">18</span>F]fluoride, which was evident in subsequent accumulation of activity in bones. Images were highly similar to those resulting from applied [<span class="elsevierStyleSup">18</span>F]fluoride.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Taken together, the examined tracers had varying properties in the embryonated chicken egg due to their bioactivity. Therefore, it could be demonstrated that this alternative model can be used as in vivo test system for PET tracer if the properties of compounds are to be explored in a living system. Although these experiments were performed in healthy chick embryos, the method could be extended to study disease models e.g. tumours on the CAM. Thus, scientists will be able to gain additional insight into the metabolic processes of this already well-established model system.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no direct financial relation to the commercial identities described and therefore declare that there is no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres289012" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec272480" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres289011" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec272479" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "F-labelled compounds" ] 1 => array:3 [ "identificador" => "sec0020" "titulo" => "Ga-labelled compounds" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Preparation of desferrioxamine conjugates" ] ] ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Labelling of proteins" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Ligand free Cu" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Preparation of embryonated chicken eggs, catheter system and tracer injection" ] 5 => array:2 [ "identificador" => "sec0045" "titulo" => "Anaesthesia and assembly during measurement" ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Imaging system and imaging protocols" ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Image analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0060" "titulo" => "Results and discussion" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0065" "titulo" => "Properties of tracers observed in experiments with chicken eggs" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "[F]FDG" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Ga citrate and Ga-albumin desferrioxamine conjugate" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Cu chloride" ] 3 => array:2 [ "identificador" => "sec0085" "titulo" => "Ga-labelled amyloid-fibril-binding antibody (Ga-B10)" ] 4 => array:2 [ "identificador" => "sec0090" "titulo" => "N-(4-[F]fluoro-6-methylpyrimidin-2-yl)-4-nitrobenzenesulphonamide" ] ] ] ] ] 7 => array:2 [ "identificador" => "sec0095" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack66783" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-05-15" "fechaAceptado" => "2013-07-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec272480" "palabras" => array:8 [ 0 => "MicroPET/CT" 1 => "In vivo" 2 => "In ovo" 3 => "Chick embryo" 4 => "Alternative model" 5 => "<span class="elsevierStyleSup">18</span>F" 6 => "<span class="elsevierStyleSup">68</span>Ga" 7 => "<span class="elsevierStyleSup">64</span>Cu tracer evaluation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec272479" "palabras" => array:8 [ 0 => "MicroPET/TC" 1 => "In vivo" 2 => "In ovo" 3 => "Embrión de pollo" 4 => "Modelo alternativo" 5 => "<span class="elsevierStyleSup">18</span>F" 6 => "<span class="elsevierStyleSup">68</span>Ga" 7 => "<span class="elsevierStyleSup">64</span>Cu evaluación trazador" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using <span class="elsevierStyleSup">18</span>F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these <span class="elsevierStyleSup">18</span>F- and <span class="elsevierStyleSup">68</span>Ga-labelled tracers and of <span class="elsevierStyleSup">64</span>Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[<span class="elsevierStyleSup">18</span>F]fluoroglucose ([<span class="elsevierStyleSup">18</span>F]FDG) was primarily absorbed at the sites of bone growth. <span class="elsevierStyleSup">64</span>Cu chloride and a <span class="elsevierStyleSup">68</span>Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La tomografía por emisión de positrones/tomografía computarizada (PET/TC) es una técnica establecida en la investigación preclínica de enfermedades en modelos de animales pequeños y en el diagnóstico clínico de cáncer. Esta técnica combina la información funcional del biomarcador emisor de positrones con los datos anatómicos de la imagen TC, permitiendo de este modo la investigación in vivo de los procesos biológicos en 4 dimensiones. Recientemente, el crecimiento de los huesos de los embriones de pollo se ha podido monitorizar usando PET/TC con <span class="elsevierStyleSup">18</span>F fluoruro como trazador óseo. Estamos interesados en la investigación de otros trazadores PET/TC en embriones de pollo como sistema de modelo in vivo. Para ello, evaluamos varios radiotrazadores usados habitualmente en pruebas clínicas o sintetizamos aquellos que no estaban disponibles comercialmente. Utilizando un microPET/TC de animales pequeños, evaluamos las características de <span class="elsevierStyleSup">18</span>F, <span class="elsevierStyleSup">68</span>Ga y <span class="elsevierStyleSup">64</span>Cu cloruro en huevos con sondaje. La 2-Deoxy-2[<span class="elsevierStyleSup">18</span>F]fluorodeoxiglucosa (<span class="elsevierStyleSup">18</span>F FDG) estaba absorbida en los sitios de crecimiento de los huesos. El <span class="elsevierStyleSup">64</span>Cu cloruro y un anticuerpo de unión a fibrillas de amiloide marcado con <span class="elsevierStyleSup">68</span>Ga se acumularon en el hígado, mientras que el <span class="elsevierStyleSup">68</span>Ga ligado a un conjugado de desferroxamina disminuyó con el tiempo en ese mismo órgano. Los resultados indican que estos biomarcadores pueden ser utilizados para la monitorización de procesos biológicos en huevos de pollo como modelo animal.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 511 "Ancho" => 1123 "Tamanyo" => 45317 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Structure of the <span class="elsevierStyleSup">18</span>F-sulphonamide (<span class="elsevierStyleBold">1</span>).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 450 "Ancho" => 1800 "Tamanyo" => 108048 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Definition of ROIs target sites. A–D based on PET-MIPs and E based on the appropriate CT slice according to the orientation by the PET-MIPs.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3840 "Ancho" => 2949 "Tamanyo" => 1614075 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">MIP of reconstructed microPET data from combined time frames. The views were arranged so that spine of embryos formed an arch at the bottom. Colours indicating high (white) and low (blue) activity were not normalised. (a) The distribution of [<span class="elsevierStyleSup">18</span>F]FDG, 1st line: arrows indicate the uptake in growth zones (white, red). 2nd line: additional application of [<span class="elsevierStyleSup">18</span>F]fluoride after 1<span class="elsevierStyleHsp" style=""></span>h, signal in bones (orange red, white arrows) and overlap between bones and growth zones (in green/yellow) after 1<span class="elsevierStyleHsp" style=""></span>h. (b) The distribution of <span class="elsevierStyleSup">68</span>Ga-labelled citrate, high liver signal (arrow) after 1–2<span class="elsevierStyleHsp" style=""></span>min. (c) The distribution of <span class="elsevierStyleSup">68</span>Ga-albumin desferrioxamine conjugate, fast liver uptake (arrow). (d) The distribution of <span class="elsevierStyleSup">68</span>Ga-labelled amyloid fibril binding antibody, accumulation in the liver. (e) The distribution of uncomplexed <span class="elsevierStyleSup">64</span>Cu chloride, fast liver uptake (arrows). (f) The distribution of <span class="elsevierStyleSup">18</span>F-sulphonamide, initial uptake in the liver (1–2<span class="elsevierStyleHsp" style=""></span>min, arrow), kidneys (4–6<span class="elsevierStyleHsp" style=""></span>min, arrow) and subsequently in skull (1<span class="elsevierStyleHsp" style=""></span>h left arrow) and bones (1<span class="elsevierStyleHsp" style=""></span>h, right arrows).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 4004 "Ancho" => 2999 "Tamanyo" => 760347 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Average time activity curves of tracers during prolonged observation periods. The corrected percentage of the injected dose per g of tissue [%ID<span class="elsevierStyleInf">corr</span>/g] was plotted against frame mid time.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scaling down imaging: molecular mapping of cancer in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. 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Journal Information
Original article
Dynamic behaviour of selected PET tracers in embryonated chicken eggs
Comportamiento dinámico de marcadores PET seleccionados en huevos de gallina embrionados
P. Gebhardta,
, L. Würbacha, A. Heidricha, L. Heinricha, M. Waltherb, T. Opfermannc, B. Sørensena, H.P. Saluza,d
Corresponding author
a Leibniz Institute for Natural Product Research and Infection Biology – Hans-Knöll-Institute, Jena, Germany
b Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
c Clinic of Nuclear Medicine, Jena University Hospital, Jena, Germany
d Friedrich Schiller University of Jena, Jena, Germany