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Purpose: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for 111In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064). We evaluated the efficacy of PSMA-tPDT using PSMA-N064 in cell viability assays, a mouse xenograft model and in an ex vivo incubation study on fresh human PCa tissue. Methods: In vitro, therapeutic efficacy of PSMA-N064 was evaluated using PSMA-positive LS174T cells and LS174T wild-type cells. In vivo, PSMA-N064-mediated tPDT was tested in immunodeficient BALB/c mice-bearing PSMA-positive LS174T xenografts. Tumor growth and survival were compared to control mice that received either NIR light or ligand injection only. Ex vivo tPDT efficacy was evaluated in excised fresh human PCa tissue incubated with PSMA-N064. Results: In vitro, tPDT led to a PSMA-specific light- and ligand dose-dependent loss in cell viability. In vivo, tPDT-induced tumor cell apoptosis, delayed tumor growth, and significantly improved survival (p = 0.004) of the treated PSMA-positive tumor-bearing mice compared with the controls. In fresh ex vivo human PCa tissue, apoptosis was significantly increased in PSMA-tPDT-treated samples compared to non-treated control samples (p = 0.037). Conclusion: This study showed the feasibility of PSMA-N064-mediated tPDT in cell assays, a xenograft model and excised fresh human PCa tissue. This paves the way to investigate the impact of in vivo PSMA-tPDT on surgical outcome in PCa patients. [ABSTRACT FROM AUTHOR]

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field, and include new PET-labelling methods for 11C and 18F, the importance of choosing the proper chelator for a given radioactive metal ion, implications of total body PET on use of radiopharmaceuticals, legislation issues and radionuclide therapy including the emerging role of 161Tb. [ABSTRACT FROM AUTHOR]

This document is intended as a supplement to the EANM "Guidelines on current Good Radiopharmacy Practice (cGRPP)" issued by the Radiopharmacy Committee of the EANM (Gillings et al. in EJNMMI Radiopharm Chem. 6:8, 2021). The aim of the EANM Radiopharmacy Committee is to provide a document that describes how to manage risks associated with small-scale "in-house" preparation of radiopharmaceuticals, not intended for commercial purposes or distribution. [ABSTRACT FROM AUTHOR]

Introduction: The first generation ligands for prostate-specific membrane antigen (PSMA)–targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA ligands by crucial modification of existing PSMA ligand backbone structures (PSMA-1007/PSMA-617) for multimodal imaging and targeted PDT of PCa. Methods: Various new PSMA ligands were synthesized using solid-phase chemistry and provided with a DOTA chelator for 111In labeling and the fluorophore/photosensitizer IRDye700DX. The performance of three new dual-labeled ligands was compared with a previously published first-generation ligand (PSMA-N064) and a control ligand with an incomplete PSMA-binding motif. PSMA specificity, affinity, and PDT efficacy of these ligands were determined in LS174T-PSMA cells and control LS174T wildtype cells. Tumor targeting properties were evaluated in BALB/c nude mice with subcutaneous LS174T-PSMA and LS174T wildtype tumors using µSPECT/CT imaging, fluorescence imaging, and biodistribution studies after dissection. Results: In order to synthesize the new dual-labeled ligands, we modified the PSMA peptide linker by substitution of a glutamic acid into a lysine residue, providing a handle for conjugation of multiple functional moieties. Ligand optimization showed that the new backbone structure leads to high-affinity PSMA ligands (all IC50 < 50 nM). Moreover, ligand-mediated PDT led to a PSMA-specific decrease in cell viability in vitro (P < 0.001). Linker modification significantly improved tumor targeting compared to the previously developed PSMA-N064 ligand (≥ 20 ± 3%ID/g vs 14 ± 2%ID/g, P < 0.01) and enabled specific visualization of PMSA-positive tumors using both radionuclide and fluorescence imaging in mice. Conclusion: The new high-affinity dual-labeled PSMA-targeting ligands with optimized backbone compositions showed increased tumor targeting and enabled multimodal image-guided PCa surgery combined with targeted photodynamic therapy. [ABSTRACT FROM AUTHOR]

Rationale: Prolonged in vivo evaluation of PSMA tracers could improve tumor imaging and patient selection for 177Lu-PSMA-617 and 177Lu-PSMA-I&T. In this study, we present the radiolabeling method of PSMA-617 and PSMA-I&T with the long-lived positron emitter 89Zr to enable PET imaging up to 7 days post-injection. We compared the biodistribution of 89Zr-PSMA-617 and 89Zr-PSMA-I&T to those of 177Lu-PSMA-617 and 177Lu-PSMA-I&T, respectively, in a PSMA+ xenograft model. Moreover, we provide the first human 89Zr-PSMA-617 images. Materials and methods: PSMA ligands were labeled with 50-55 MBq [89Zr]ZrCl4 using a two-step labeling protocol. For biodistribution, BALB/c nude mice bearing PSMA+ and PSMA− xenografts received 0.6 µg (0.6–1 MBq) of 89Zr-PSMA-617, 89Zr-PSMA-I&T, 177Lu-PSMA-617, or 177Lu-PSMA-I&T intravenously. Ex vivo biodistribution and PET/SPECT imaging were performed up to 168 h post-injection. Dosimetry was performed from the biodistribution data. The patient received 90.5 MBq 89Zr-PSMA-617 followed by PET/CT imaging. Results: 89Zr-labeled PSMA ligands showed a comparable ex vivo biodistribution to its respective 177Lu-labeled counterparts with high tumor accumulation in the PSMA+ xenografts. However, using a dose estimation model for 177Lu, absorbed radiation dose in bone and kidneys differed among the 177Lu-PSMA and 89Zr-PSMA tracers. 89Zr-PSMA-617 PET in the first human patient showed high contrast of PSMA expressing tissues up to 48 h post-injection. Conclusion: PSMA-617 and PSMA-I&T were successfully labeled with 89Zr and demonstrated high uptake in PSMA+ xenografts, which enabled PET up to 168 h post-injection. The biodistribution of 89Zr-PSMA-I&T and 89Zr-PSMA-617 resembled that of 177Lu-PSMA-I&T and 177Lu-PSMA-617, respectively. The first patient 89Zr-PSMA-617 PET images were of high quality warranting further clinical investigation. [ABSTRACT FROM AUTHOR]

Background: The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. Results: [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. Conclusion: To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff. [ABSTRACT FROM AUTHOR]

This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. It is intended for non-commercial sites such as hospital radiopharmacies, nuclear medicine departments, research PET centres and in general any healthcare establishments. In the first section, general aspects which are applicable to all levels of operations are discussed. The second section discusses the preparation of small-scale radiopharmaceuticals (SSRP) using licensed generators and kits. Finally, the third section goes into the more complex preparation of SSRP from non-licensed starting materials, often requiring a purification step and sterile filtration. The intention is that the guideline will assist radiopharmacies in the preparation of diagnostic and therapeutic SSRP's safe for human administration. [ABSTRACT FROM AUTHOR]

Background: To fulfil good manufacturing requirements, analytical methods for the analysis of pharmaceuticals for human and vetinary use must be validated. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has published guidance documents on the requirements for such validation activities and these have been adopted by the European Medicines Agency, The U.S. Food and Drug Administration (FDA) and other regulatory bodies. These guidance documents do not, however, fully address all the specific tests required for the analysis of radiopharmaceuticals. This guideline attempts to rectify this shortcoming, by recommending approaches to validate such methods. Results: Recommedations for the validation of analytical methods which are specific for radiopharmaceutials are presented in this guideline, along with two practical examples. Conclusions: In order to comply with good manufacturing practice, analytical methods for radiopharmaceuticals for human use should be validated. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.Procedures: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [18F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.Results: 5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [18F]FLT SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUVmax at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats.Conclusion: This study suggests that 5-FU treatment induces a flare in [18F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmean did not change significantly. Future studies in larger groups are warranted to further investigate whether [18F]FLT PET can discriminate between disease progression and treatment response. [ABSTRACT FROM AUTHOR]

Purpose: Multimeric arginine-glycine-aspartic acid (RGD) peptides have advantages for imaging integrin αvβ3 expression. Here, we compared the in vitro and in vivo behavior of three different Ga-68-labeled multimeric Fusarinine C-RGD (FSC-RGD) conjugates, whereby RGD was coupled directly, via a succinic acid or PEG linker (FSC(RGDfE)3, FSC(succ-RGD)3, FSC(Mal-RGD)3). The positron emission tomography/X-ray computed tomography (PET/CT) imaging properties were further compared using [(68)Ga]FSC(succ-RGD)3 with the monomeric [(68)Ga]NODAGA-RGD in a murine tumor model.Procedure: FSC-RGD conjugates were labeled with Ga-68, and stability properties were studied. For in vitro characterization, the partition coefficient, integrin αvβ3 binding affinity, and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET/CT were carried out using mice bearing either human M21/M21-L melanoma or human U87MG glioblastoma tumor xenografts.Results: All FSC-RGD conjugates were quantitatively labeled with Ga-68 within 10 min at RT. The [(68)Ga]FSC-RGD conjugates exhibited high stability and hydrophilic character, with only minor differences between the different conjugates. In vitro and in vivo studies showed enhanced integrin αvβ3 binding affinity, receptor-selective tumor uptake, and rapid renal excretion resulting in good imaging properties.Conclusions: The type of linker between FSC and RGD had no pronounced effect on targeting properties of [(68)Ga]FSC-RGD trimers. In particular, [(68)Ga]FSC(succ-RGD)3 exhibited improved properties compared to [(68)Ga]NODAGA-RGD, making it an alternative for imaging integrin αvβ3 expression. [ABSTRACT FROM AUTHOR]

OP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targets V. Radchenko, J.W. Engle, C. Roy, J. Griswold, M.F. Nortier, E.R. Birnbaum, M. Brugh, S. Mirzadeh, K. D. John, M.E. Fassbender OP04 Comparison of [68Ga]FSC(succ-RGD)3 and [68Ga]NODAGA-RGD for PET imaging of αvβ3 integrin expression Chuangyan Zhai, Gerben M. Franssen, Milos Petrik, Peter Laverman, Clemens Decristoforo OP05 A new NPY-Y1R targeting peptide for breast cancer PET imaging Ait-Mohand Samia, Dumulon-Perreault Véronique, Guérin Brigitte OP06 The influence of multivalency on CCK 2 receptor targeting D. Summer, A. Kroess, C. Rangger, H. Haas, P. Laverman, F. Gerben, E. von Guggenberg, C.Decristoforo OP07 SPECT Imaging of αvβ3 Expression by [99mTc(N)PNP43]- Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5 Cristina Bolzati, Nicola Salvarese, Fiorenzo Refosco, Laura Meléndez-Alafort, Debora Carpanese, Antonio Rosato, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura Zaccaro OP09 New dienophiles for the inverse-electron-demand Diels-Alder reaction and for pretargeted PET imaging Emilie Billaud, Muneer Ahamed, Frederik Cleeren, Elnaz Shahbazali, Tim Noël, Volker Hessel, Alfons Verbruggen and Guy Bormans OP10 New complexing agent for Al18F-labelling of heat-sensitive biomolecules: Synthesis and preclinical evaluation of Al18F-RESCA1-HAS Cleeren F, Lecina J, Koole M, Verbruggen A and Bormans G OP11 A novel versatile precursor efficient for F-18 radiolabelling via click-chemistry B. Lugatoa, S. Stucchia, E.A. Turollaa, L. Giulianoa, S.Toddea, P. Ferraboschib OP12 A general applicable method to quantify unidentified UV impurities in radiopharmaceuticals R.P. Klok, M.P.J. Mooijer, N.H. Hendrikse, A.D. Windhorst OP13 Development of [F]Fluoro-C-glycosides to radiolabel peptides Collet C., Petry N., Chrétien F., Karcher G., Pellegrini-Moïse N., Lamandé-Langle S. OP14 A Microfluidic Approach for the 68Ga-labeling of PSMAHBED-CC and NODAGA-RGD Sarah Pfaff, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak OP16 Surprising reactivity of astatine in the nucleophilic substitution of aryliodonium salts: application to the radiolabeling of antibodies François Guérard, Yong-Sok Lee, Sébastien Gouard, Kwamena Baidoo, Cyrille Alliot, Michel Chérel, Martin W. Brechbiel, Jean-François Gestin OP17 Cu-NOTA-pertuzumab F(ab') fragments, a second-generation probe for PET imaging of the response of HER2-positive breast cancer to trastuzumab (Herceptin) Lam K, Chan C, Reilly RM OP18 Development of radiohalogenated analogues of a avb6-specific peptide for high LET particle emitter targeted radionuclide therapy of cancer Salomé Paillas, John Marshall, Jean-Pierre Pouget, Jane Sosabowski OP19 Ligand Specific Efficiency (LSE) as a guide in tracer optimization Emmanuelle Briard, Yves P. Auberson, John Reilly, Mark Healy, David Sykes OP23 The radiosynthesis of an 18F-labeled triglyceride, developed to visualize and quantify brown adipose tissue activity Andreas Paulus, Wouter van Marken Lichtenbelt,Felix Mottaghy, Matthias Bauwens OP24 Influence of the fluorescent dye on the tumor targeting properties of dual-labeled HBED-CC based PSMA inhibitors Baranski, Ann-Christin, Schäfer, Martin, Bauder-Wüst, Ulrike, Haberkorn, Uwe, Eder, Matthias, Kopka, Klaus OP25 [18F]MEL050 as a melanin PET tracer : fully automated radiosynthesis and evaluation for the detection of pigmented melanoma in mice pulmonary metastases Chaussard M, Hosten B, Vignal N, Tsoupko-Sitnikov V, Hernio N, Hontonnou F, Merlet P, Poyet JL, Sarda-Mantel L, Rizzo-Padoin N OP26 Design and Preclinical Evaluation of Novel Radiofluorinated PSMA Targeting Ligands Based on PSMA-617 J. Cardinale, M. Schäfer, M. Benešová, U. Bauder-Wüst, O. Seibert, F. Giesel, U. Haberkorn, M. Eder, K. Kopka OP27 A novel radiolabeled peptide for PET imaging of prostate cancer: 64Cu-DOTHA2-PEG-RM26 Mansour Nematallah, Paquette Michel, Ait-Mohand Samia, Dumulon-Perreault Véronique, Lecomte Roger, Guérin Brigitte OP29 Biodistribution of [F]Amylovis®, a new radiotracer PET imaging of β-amyloid plaques Fernandez-Maza L, Rivera-Marrero S, Prats Capote A, Parrado-Gallego A, Fernandez-Gomez I, Balcerzyk M, Sablon-Carrazana M, Perera-Pintado A, Merceron-Martinez D, Acosta-Medina E, Rodriguez-Tanty C OP30 Synthesis and preclinical evaluation of [11C]-BA1 PET tracer for the imaging of CSF-1R Bala Attili, Muneer Ahamed, Guy Bormans OP31 In vivo imaging of the MCHR1 in the ventricular system via [18F]FE@SNAP C. Philippe, M. Zeilinger, T. Scherer, C. Fürnsinn, M. Dumanic, W. Wadsak, M. Hacker, M. Mitterhauser OP32 Synthesis of the first carbon-11 labelled P2Y12 receptor antagonist for imaging the anti-inflammatory phenotype of activated microglia B. Janssen, D.J. Vugts, G.T. Molenaar, U. Funke, P.S. Kruijer, F. Dollé, G. Bormans, A.A. Lammertsma, A.D. Windhorst OP33 Radiosynthesis of a selective HDAC6 inhibitor [11C]KB631 and in vitro and ex vivo evaluation Koen Vermeulen, Muneer Ahamed, Michael Schnekenburger, Mathy Froeyen, Dag Erlend Olberg, Marc Diederich, Guy Bormansa OP34 Improving metabolic stability of fluorine-18 labelled verapamil analogues Raaphorst RM, Luurtsema G, Lammertsma AA, Elsinga PH, Windhorst AD OP36 Development of a novel PET tracer for the activin receptor-like kinase 5 Lonneke Rotteveel, Uta Funke, Peter ten Dijke, Harm Jan Bogaard, Adriaan A. Lammertsma, Albert D. Windhorst OP37 SPECT imaging and biodistribution studies of 111In-EGF-Au-PEG nanoparticles in vivo Lei Song, Sarah Able, Nadia Falzone, Veerle Kersemans, Katherine Vallis OP38 Melanoma targeting with [99mTc(N)(PNP3)]-labeled NAPamide derivatives: preliminary pharmacological studies Davide Carta, Nicola Salvarese, Wiebke Sihver, Feng Gao, Hans Jürgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Cristina Bolzati OP39 [Ga]NODAGA-RGD: cGMP synthesis and data from a phase I clinical study Roland Haubner, Armin Finkensted, Armin Stegmair, Christine Rangger, Clemens Decristoforo, Heinz Zoller, Irene J. Virgolin OP44 Implementation of a GMP-grade radiopharmacy facility in Maastricht Ivo Pooters, Maartje Lotz, Roel Wierts, Felix Mottaghy, Matthias Bauwens OP45 Setting up a GMP production of a new radiopharmaceutical Forsback, Sarita, Bergman Jörgen, Kivelä Riikka OP48 In vitro and in vivo evaluation of 68-gallium labeled Fe3O4-DPD nanoparticles as potential PET/MRI imaging agents M. Karageorgou, M. Radović, C. Tsoukalas, B. Antic, M. Gazouli, M. Paravatou-Petsotas, S. Xanthopouls, M. Calamiotou, D. Stamopoulos, S. Vranješ-Durić, P. Bouziotis OP49 Fast PET imaging of inflammation using 68Ga-citrate with Fe-containing salts of hydroxy acids A. S. Lunev, A. A. Larenkov, K.A. Petrosova, O. E. Klementyeva, G. E. Kodina PP01 Installation and validation of 11C-methionine synthesis Kvernenes, O.H., Adamsen, T.C.H. PP02 Fully automated synthesis of 68Ga-labelled peptides using the IBA Synthera® and Synthera® Extension modules René Martin, Sebastian Weidlich, Anna-Maria Zerges, Cristiana Gameiro, Neva Lazarova, Marco Müllera PP03 GMP compliant production of O-labeled water using IBA 18 MeV proton cyclotron Gert Luurtsema, Michèl de Vries, Michel Ghyoot, Gina van der Woude, Rolf Zijlma, Rudi Dierckx, Hendrikus H. Boersma, Philip H. Elsinga PP04 In vitro Nuclear Imaging Potential of New Subphthalocyanine and Zinc Phthalocyanine Fatma Yurt Lambrecht, Ozge Er, Mine Ince, Cıgır Biray Avci, Cumhur Gunduz, Fatma Aslihan Sarı PP05 Synthesis, Photodynamic Therapy Efficacy and Nuclear Imaging Potential of Zinc Phthalocyanines Kasim Ocakoglu, Ozge Er, Onur Alp Ersoz, Fatma Yurt Lambrecht, Mine Ince, Cagla Kayabasi, Cumhur Gunduz PP06 Radio-U(H)PLC - the Search on the Optimal Flow Cell for the γ-Detector Torsten Kniess, Sebastian Meister, Steffen Fischer, Jörg Steinbach PP07 Radiolabeling, characterization & biodistribution study of cysteine and its derivatives with Tc99m Rabia Ashfaq, Saeed Iqbal, Atiq-ur-Rehman, Irfan ullah Khan PP08 Radiolabelling of poly (lactic-co.glycolic acid) (PLGA) nanoparticles with 99mTC R Iglesias-Jerez, Cayero-Otero, L. Martín-Banderas, A. Perera-Pintado, I. Borrego-Dorado PP09 Development of [F]PD-410 as a non-peptidic PET radiotracer for gastrin releasing peptide receptors Ines Farinha-Antunes, Chantal Kwizera, Enza Lacivita, Ermelinda Lucente, Mauro Niso, Paola De Giorgio, Roberto Perrone, Nicola A. Colabufo, Philip H. Elsinga, Marcello Leopoldo PP10 An improved nucleophilic synthesis of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy) benzothiazole ([18F]FEDMBT), potential diagnostic agent for breast cancer imaging by PET V.V. Vaulina, O.S. Fedorova, V.V. Orlovskaja, С.L. Chen, G.Y. Li, F.C. Meng, R.S. Liu, H.E. Wang, R.N. Krasikova PP11 Internal radiation dose assessment of radiopharmaceuticals prepared with accelerator-produced 99mTc Laura Meléndez-Alafort, Mohamed Abozeid, Guillermina Ferro-Flores, Anna Negri, Michele Bello, Nikolay Uzunov, Martha Paiusco, Juan Esposito, Antonio Rosato PP12 A specialized five-compartmental model software for pharmacokinetic parameters calculation Laura Meléndez-Alafort, Cristina Bolzati, Guillermina Ferro-Flores, Nicola Salvarese, Debora Carpanese, Mohamed Abozeid, Antonio Rosato, Nikolay Uzunov PP13 Molecular imaging of the pharmacokinetic behavior of low molecular weight F-labeled PEtOx in comparison to Zr-labeled PEtOx Palmieri L, Verbrugghen T, Glassner M, Hoogenboom R, Staelens S, Wyffels L PP14 Towards nucleophilic synthesis of the α-[18F]fluoropropyl-L-dihydroxyphenylalanine V. V. Orlovskaja, O. F. Kuznetsova, O. S. Fedorova, V. I. Maleev, Yu. N. Belokon, A. Geolchanyan, A. S. Saghyan, L. Mu, R. Schibli, S. M. Ametamey, R. N. Krasikova PP15 A convenient one-pot synthesis of [18F]clofarabine Revunov, Evgeny, Malmquist, Jonas, Johnström, Peter, Van Valkenburgh, Juno, Steele, Dalton, Halldin, Christer, Schou, Magnus PP16 BODIPY-estradiol conjugates as multi-modality tumor imaging agents Samira Osati,Michel Paquette,Simon Beaudoin,Hasrat Ali,Brigitte Guerin, Jeffrey V. Leyton, Johan E. van Lier PP17 Easy and high yielding synthesis of 68Ga-labelled HBED-PSMA and DOTA-PSMA by using a Modular-Lab Eazy automatic synthesizer Di Iorio V, Iori M, Donati C, Lanzetta V, Capponi PC, Rubagotti S, Dreger T, Kunkel F, Asti M PP18 Synthesis and evaluation of fusarinine C-based octadentate bifunctional chelators for zirconium-89 labelling Chuangyan Zhai, Christine Rangger, Dominik Summer, Hubertus Haas, Clemens Decristoforo PP19 Fully automated production of [18F]NaF using a re-configuring FDG synthesis module. Suphansa Kijprayoon, Ananya Ruangma, Suthatip Ngokpol, Samart Tuamputsha PP20 Extension of the Carbon-11 Small Labeling Agents Toolbox and Conjugate Addition Ulrike Filp, Anna Pees, Carlotta Taddei, Aleksandra Pekošak, Antony D. Gee, Alex J. Poot, Albert D. Windhorst PP21 In vitro studies on BBB penetration of pramipexole encapsulated theranostic liposomes for the therapy of Parkinson's disease Mine Silindir Gunay, A. Yekta Ozer, Suna Erdogan, Ipek Baysal, Denis Guilloteau, Sylvie Chalon PP22 Factors affecting tumor uptake of 99mTc-HYNIC-VEGF165 Filippo Galli, Marco Artico, Samanta Taurone, Enrica Bianchi, Bruce D. Weintraub, Mariusz Skudlinski, Alberto Signore PP23 Rhenium-188: a suitable radioisotope for targeted radiotherapy Nicolas Lepareur, Nicolas Noiret, François Hindré, Franck Lacœuille, Eric Benoist, Etienne Garin PP24 Preparation of a broad palette of 68Ga radiopharmaceuticals for clinical applications Trejo-Ballado F, Zamora-Romo E, Manrique-Arias JC, Gama-Romero HM, Contreras-Castañon G, Tecuapetla-Chantes RG, Avila-Rodriguez MA PP25 68Ga-peptide preparation with the use of two 68Ge/68Ga-generators H. Kvaternik, D. Hausberger, C. Zink, B. Rumpf, R. M. Aigner PP26 Assay of HEPES in 68Ga-peptides by HPLC H. Kvaternik, D. Hausberger, B. Rumpf, R. M. Aigner PP27 Preparation, in vitro and in vivo evaluation of a 99mTc(I)-Diethyl Ester (S,S)-Ethylenediamine- N,N´-DI-2-(3-Cyclohexyl) Propionic acid as a target-specific radiopharmaceutical Drina Janković, Mladen Lakić, Aleksandar Savić, Slavica Ristić, Nadežda Nikolić, Aleksandar Vukadinović, Tibor J. Sabo, Sanja Vranješ-Đurić PP28 90Y-labeled magnetite nanoparticles for possible application in cancer therapy S. Vranješ-Đurić, M. Radović, D. Janković, N. Nikolić, G. F. Goya, P. Calatayud, V. Spasojević, B. Antić PP29 Simplified automation of the GMP production of 68Ga-labelled peptides David Goblet, Cristiana Gameiro, Neva Lazarova PP30 Combining commercial production of multi-products in a GMP environment with Clinical & R&D activities Cristiana Gameiro, Ian Oxley, Antero Abrunhosa, Vasko Kramer, Maria Vosjan, Arnold Spaans PP31 mTc(CO)3-labeling and Comparative In-Vivo Evaluation of Two Clicked cRGDfK Peptide Derivatives Kusum Vats, Drishty Satpati, Haladhar D Sarma, Sharmila Banerjee PP32 Application of AnaLig resin for 99mTc separation from molybdenum excess Wojdowska W., Pawlak D.W., Parus L. J., Garnuszek P., Mikołajczak R. PP33 Constraints for selection of suitable precursor for one-step automated synthesis of [18F]FECNT, the dopamine transporter ligand Pijarowska-Kruszyna J, Jaron A, Kachniarz A, Malkowski B, Garnuszek P, Mikolajczak R PP34 Gamma scintigraphy studies with 99mTc- amoxicillin sodium in bacterially infected and sterile inflamed rats Derya Ilem-Ozdemir, Oya Caglayan-Orumlu, Makbule Asikoglu PP35 Preparation of 99mTc- Amoxicillin Sodium Lyophilized Kit Derya Ilem-Ozdemir, Oya Caglayan-Orumlu, Makbule Asikoglu PP36 Outfits of Tracerlan FXC-PRO for 11C-Labeling Arponen Eveliina, Helin Semi, Saarinen Timo, Vauhkala Simo, Kokkomäki Esa, Lehikoinen Pertti PP37 Microfluidic synthesis of ω-[18F]fluoro-1-alkynes Mariarosaria De Simone, Giancarlo Pascali, Ludovica Carzoli, Mauro Quaglierini, Mauro Telleschi, Piero A. Salvadori PP38 Automated 18F-flumazenil production using chemically resistant disposable cassettes Phoebe Lam, Martina Aistleitner, Reinhard Eichinger, Christoph Artner PP39 The effect of the eluent solutions (TBAHCO3, Kryptand K2.2.2) on the radiochemical yields of 18F-Fluoromethylcholine Surendra Nakka, Hemantha Kumara MC, Al-Qahtani Mohammed PP40 [68Ga]Radiolabeling of short peptide that has a PET imaging potentials Al-Qahtani, Mohammed, Al-Malki, Yousif PP41 Is validation of radiochemical purity analysis in a public hospital in a developing country possible? N Mambilima, SM Rubow PP42 Improved automated radiosynthesis of [18F]FEPPA N. Berroterán-Infante, M. Hacker, M. Mitterhauser, W. Wadsak PP43 Synthesis and initial evaluation of Al18F-RESCA1-TATE for somatostatin receptor imaging with PET Uta Funke, Frederik Cleeren, Joan Lecina, Rodrigo Gallardo, Alfons M. Verbruggen, Guy Bormans PP44 Radiolabeling and SPECT/CT imaging of different polymer-decorated zein nanoparticles for oral administration Rocío Ramos-Membrive, Ana Brotons, Gemma Quincoces, Laura Inchaurraga, Inés Luis de Redín, Verónica Morán, Berta García-García, Juan Manuel Irache, Iván Peñuelas PP45 An analysis of the quality of 68Ga-DOTANOC radiolabelling over a 3 year period Trabelsi, M., Cooper M.S. PP46 In vivo biodistribution of adult human mesenchymal stem cells I (MSCS-ah) labeled with 99MTC-HMPAO administered via intravenous and intra-articular in animal model. Preliminary results Alejandra Abella, Teodomiro Fuente, Antonio Jesús Montellano, Teresa Martínez, Ruben Rabadan, Luis Meseguer-Olmo PP47 Synthesis of [F]F-exendin-4 with high specific activity Lehtiniemi P, Yim C, Mikkola K, Nuutila P, Solin O PP48 Experimental radionuclide therapy with 177Lu-labelled cyclic minigastrin and human dosimetry estimations von Guggenberg E, Rangger C, Mair C, Balogh L, Pöstényi Z, Pawlak D, Mikołajczak R PP49 Synthesis of radiopharmaceuticals for cell radiolabelling using anion exchange column Socan A, Kolenc Peitl P, Krošelj M, Rangger C, Decristoforo C PP50 [68Ga]peptide production on commercial synthesiser mAIO Collet C., Remy S., Didier R,Vergote T.,Karcher G., Véran N. PP51 Dry kit formulation for efficient radiolabeling of 68Ga-PSMA D. Pawlak, M. Maurin, P. Garnuszek, U. Karczmarczyk, R. Mikołajczak PP52 Development of an experimental method using Cs-131 to evaluate radiobiological effects of internalized Auger-electron emitters Pil Fredericia, Gregory Severin, Torsten Groesser, Ulli Köster, Mikael Jensen PP53 Preclinical comparative evaluation of NOTA/NODAGA/DOTA CYCLO-RGD peptides labelled with Ga-68 R. Leonte, F. D. Puicea, A. Raicu, E. A. Min, R. Serban, G. Manda, D. Niculae PP54 Synthesizer- and Kit-based preparation of prostate cancer imaging agent 68Ga-RM2 Marion Zerna, Hanno Schieferstein, Andre Müller, Mathias Berndt PP55 Synthesis of pancreatic beta cell-specific [18F]fluoro-exendin-4 via strain-promoted aza-dibenzocyclooctyne/azide cycloaddition Cheng-Bin Yim, Kirsi Mikkola, Pirjo Nuutila, Olof Solin PP56 Automated systems for radiopharmacy D. Seifert, J. Ráliš, O. Lebeda PP57 Simple, suitable for everyday routine use quality control method to assess radionuclidic purity of cyclotron-produced 99mTc Svetlana V. Selivanova, Helena Senta, Éric Lavallée, Lyne Caouette, Éric Turcotte, Roger Lecomte PP58 Effective dose estimation using Monte Carlo simulation for patients undergoing radioiodine therapy Marina Zdraveska Kochovska, Emilija Janjevik Ivanovska, Vesna Spasic Jokic PP59 Chemical analysis of the rituximab radioimmunoconjugates in lyophilized formulations intended for oncological applications Darinka Gjorgieva Ackova, Katarina Smilkov, Petre Makreski, Trajče Stafilov, Emilija Janevik-Ivanovska PP61 The need and benefits of established radiopharmacy in developing African countries Aschalew Alemu, Joel Munene Muchira, David Mwanza Wanjeh, Emilija Janevik-Ivanovska PP62 University Master Program of Radiopharmacy - step forward for Good Radiopharmacy Education Emilija Janevik-Ivanovska, Zoran Zdravev, Uday Bhonsle, Osso Júnior João Alberto, Adriano Duatti, Bistra Angelovska, Zdenka Stojanovska, Zorica Arsova Sarafinovska, Darko Bosnakovski, Darinka Gorgieva-Ackova, Katarina Smilkov, Elena Drakalska, Meera Venkatesh, Rubin Gulaboski PP63 Synthesis and preclinical validations of a novel 18F-labelled RGD peptide prepared by ligation of a 2-cyanobenzothiazole with 1,2-aminothiol to image angiogenesis. Didier J. Colin, James A. H. Inkster, Stéphane Germain, Yann Seimbille [ABSTRACT FROM AUTHOR]

Purpose: A strategy not usually used to improve carrier-mediated delivery of therapeutic enzymes is the attachment of the enzymes to the outer surface of liposomes. The aim of our work was to design a new type of enzymosomes with a sufficient surface-exposed enzyme load while preserving the structural integrity of the liposomal particles and activity of the enzyme. Methods: The therapeutic antioxidant enzyme superoxide dismutase (SOD) was covalently attached to the distal terminus of polyethylene glycol (PEG) polymer chains, located at the surface of lipid vesicles, to obtain SOD-enzymosomes. Results: The in vivo fate of the optimized SOD-enzymosomes showed that SOD attachment at the end of the activated PEG slightly reduced the residence time of the liposome particles in the bloodstream after IV administration. The biodistribution studies showed that SOD-enzymosomes had a similar organ distribution profile to liposomes with SOD encapsulated in their aqueous interior (SOD-liposomes). SOD-enzymosomes showed earlier therapeutic activity than both SOD-liposomes and free SOD in rat adjuvant arthritis. SOD-enzymosomes, unlike SOD-liposomes, have a therapeutic effect, decreasing liver damage in a rat liver ischemia/reperfusion model. Conclusions: SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases. [ABSTRACT FROM AUTHOR]

Purpose: (68)Ga-triacetylfusarinine C ((68)Ga-TAFC) and (68)Ga-ferrioxamine E ((68)Ga-FOXE) showed excellent targeting properties in Aspergillus fumigatus rat infection model. Here, we report on the comparison of specificity towards different microorganisms and human lung cancer cells (H1299).Procedures: The in vitro uptake of (68)Ga-TAFC and (68)Ga-FOXE was studied in various fungal, bacterial and yeast cultures as well as in H1299 cells. The in vivo imaging was studied in fungal and bacterial rat infection and inflammation models.Results: (68)Ga-TAFC and (68)Ga-FOXE showed rapid uptake in A. fumigatus cultures, significantly lower in other fungal species and almost no uptake in other microorganisms and H1299 cells, except for (68)Ga-FOXE in Staphylococcus aureus. (68)Ga-TAFC and (68)Ga-FOXE revealed rapid uptake in the lungs of A. fumigatus-infected rats, low accumulation in sterile inflammation and no uptake in bacterial abscess.Conclusions: We have shown that (68)Ga-FOXE and (68)Ga-TAFC have high uptake in A. fumigatus both in vitro and in vivo. (68)Ga-TAFC showed higher specificity, while (68)Ga-FOXE showed higher sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: Ga-triacetylfusarinine C (Ga-TAFC) and Ga-ferrioxamine E (Ga-FOXE) showed excellent targeting properties in Aspergillus fumigatus rat infection model. Here, we report on the comparison of specificity towards different microorganisms and human lung cancer cells (H1299). Procedures: The in vitro uptake of Ga-TAFC and Ga-FOXE was studied in various fungal, bacterial and yeast cultures as well as in H1299 cells. The in vivo imaging was studied in fungal and bacterial rat infection and inflammation models. Results: Ga-TAFC and Ga-FOXE showed rapid uptake in A. fumigatus cultures, significantly lower in other fungal species and almost no uptake in other microorganisms and H1299 cells, except for Ga-FOXE in Staphylococcus aureus. Ga-TAFC and Ga-FOXE revealed rapid uptake in the lungs of A. fumigatus-infected rats, low accumulation in sterile inflammation and no uptake in bacterial abscess. Conclusions: We have shown that Ga-FOXE and Ga-TAFC have high uptake in A. fumigatus both in vitro and in vivo. Ga-TAFC showed higher specificity, while Ga-FOXE showed higher sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). Methods: Siderophores were labelled with Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic μPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. Results: Ga-siderophores were labelled with high radiochemical purity and specific activity. Ga-TAFC and Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, Ga-TAFC and Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by μPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. Conclusion: Ga-TAFC and Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging. [ABSTRACT FROM AUTHOR]

Purpose: Targeting of cholecystokinin receptor expressing malignancies such as medullary thyroid carcinoma is currently limited by low in vivo stability of radioligands. To increase the stability, we have developed and preclinically evaluated two cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-minigastrin analogs radiolabeled with In and Ga. Procedures: Radiolabeling efficiency, in vitro characterization, cholecystokinin receptor subtype 2 (CCK-2) binding in human tumor tissues, and cell internalization on CCK-2 receptor expressing AR42J cells, as well as biodistribution and small animal imaging in two different mouse xenograft models were studied. Results: High receptor affinity and receptor-mediated uptake of the radioligands in AR42J cells was confirmed in vitro. In-labeled cyclic DOTA-peptides showed a specific tumor uptake of ~1% ID/g in vivo,Ga-labeled analogs of ~3% ID/g. Small animal SPECT imaging resulted to be superior with In-DOTA-cyclo-MG2 in comparison with In-DOTA-cyclo-MG1. Conclusions: Cyclic DOTA-minigastrin analogs are promising candidates for gastrin receptor scintigraphy and targeted radionuclide therapy. [ABSTRACT FROM AUTHOR]

We recently reported a facile method based on the chelation of [F]aluminum fluoride (AlF) by NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). Here, we present a further optimization of the F labeling of NOTA-octreotide (IMP466). Octreotide was conjugated with the NOTA chelate and was labeled with F in a two-step, one-pot method. The labeling procedure was optimized with regard to the labeling buffer, ionic strength, peptide concentration, and temperature. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of F-IMP466 was studied in AR42J tumor-bearing mice. In addition, microPET/CT images were acquired. IMP466 was labeled with AlF in a single step with 97% yield in the presence of 80% ( v/ v) acetonitrile or ethanol. The labeled product was purified by HPLC to remove unlabeled peptide and unbound AlF. The radiolabeling, including purification, was performed for 45 min. Specific activities of 48,000 GBq/mmol could be obtained. F-IMP466 showed a high tumor uptake and excellent tumor-to-blood ratios at 2 h post-injection. In addition, the low bone uptake indicated that the AlF-NOTA complex was stable in vivo. PET/CT scans revealed excellent tumor delineation and specific accumulation in the tumor. Uptake in receptor-negative organs was low. NOTA-octreotide could be labeled with F in quantitative yields using a rapid two-step, one-pot, method. The compound was stable in vivo and showed rapid accretion in SSTR-receptor-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds such as RGD peptides, GRPR-binding peptides, and Affibody molecules with F. [ABSTRACT FROM AUTHOR]

Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The In-labelled somatostatin analogue octreotide (OctreoScan™) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. [ABSTRACT FROM AUTHOR]

Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, like medullary thyroid carcinomas, small cell lung cancers and stromal ovarian cancers. The specific receptor-binding property of the endogenous ligands for these receptors can be exploited by labeling peptides with a radionuclide and using these as carriers to guide the radioactivity to the tissues that express the receptors. In this way, tumors can be visualized using positron emission tomography and single photon emission computed tomography imaging. A variety of radiolabeled CCK/gastrin-related peptides has been synthesized and characterized for imaging. All peptides have the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-Phe-NH in common or derivatives thereof. This review focuses on the development and application of radiolabeled CCK/gastrin peptides for radionuclide imaging and radionuclide therapy of tumors expressing CCK receptors. We discuss both preclinical studies as well as clinical studies with CCK and gastrin peptides. [ABSTRACT FROM AUTHOR]

Purpose: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. Methods: Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. Results: Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. Conclusion: Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may therefore be good candidates for future clinical studies. [ABSTRACT FROM AUTHOR]

Tumour cell hypoxia is a common feature in solid tumours adversely affecting radiosensitivity and chemosensitivity in head and neck squamous cell carcinomas. Positron emission tomography (PET) using the tracer [18F]fluoromisonidazole ([18F]FMISO) is most frequently used for non-invasive evaluation of hypoxia in human tumours. A series of ten human head and neck xenograft tumour lines was used to validate [18F]FMISO as hypoxia marker at the microregional level. Autoradiography after injection of [18F]FMISO was compared with immunohistochemical staining for the hypoxic cell marker pimonidazole in the same tumour sections of ten different human head and neck xenograft tumour lines. The methods were compared: first, qualitatively considering the microarchitecture; second, by obtaining a pixel-by-pixel correlation of both markers at the microregional level; third, by measuring the signal intensity of both images; and fourth, by calculating the hypoxic fractions by pimonidazole labelling. The pattern of [18F]FMISO signal was dependent on the distribution of hypoxia at the microregional level. The comparison of [18F]FMISO autoradiography and pimonidazole immunohistochemistry by pixel-by-pixel analysis revealed moderate correlations. In five tumour lines, a significant correlation between the mean [18F]FMISO and pimonidazole signal intensity was found (range, r 2 = 0.91 to r 2 = 0.99). Comparison of the tumour lines with respect to the microregional distribution pattern of hypoxia revealed that the correlation between the mean signal intensities strongly depended on the microarchitecture. Overall, a weak but significant correlation between hypoxic fractions based on pimonidazole labeling and the mean [18F]FMISO signal intensity was observed ( r 2 = 0.18, p = 0.02). For the three tumour models with a ribbon-like microregional distribution pattern of hypoxia, the correlation between the hypoxic fraction and the mean [18F]FMISO signal intensity was much stronger and more significant ( r 2 = 0.73, p < 0.001) than for the tumours with a more homogenous, patchy, microregional distribution pattern of hypoxia. Different patterns of [18F]FMISO accumulation dependent on the underlying microregional distribution of hypoxia were found in ten head and neck xenograft tumours. A weak albeit significant correlation was found between the mean [18F]FMISO signal intensity and the hypoxic fraction of the tumours. In larger clinical tumours, [18F]FMISO–PET provides information on the tumour oxygenation status on a global level, facilitating dose painting in radiation treatment planning. However, caution must be taken when studying small tumour subvolumes as accumulation of the tracer depends on the presence of hypoxia and on the tumour microarchitecture. [ABSTRACT FROM AUTHOR]

Radiolabelled cholecystokinin (CCK) and gastrin-derived peptides potentially can be used for peptide receptor radionuclide therapy (PRRT). Recently, a splice variant version of the CCK2R has been identified, designated CCK2i4svR. Constitutive expression of this receptor has been demonstrated in human colorectal cancer and in pancreatic cancer, but not in normal tissue. So far, it has never been shown whether radiolabelled peptides can target the CCK2i4svR in vivo. In this paper, we investigated the potential of sulfated 111In-labelled DOTA-CCK8 (sCCK8), a pan-CCKR-binding peptide, and [111In]DOTA-minigastrin (MG0), a CCK2R selective peptide, for the targeting of the CCK2i4svR. The receptor binding affinity of [111In]DOTA-sCCK8 and [111In]DOTA-MG0 for the CCK2R and CCK2i4svR was determined using stably transfected HEK293 cell lines, expressing either CCK2R or CCK2i4svR. Tumour targeting was studied in HEK293-CCK2i4svR tumour-bearing athymic mice. [111In]DOTA-sCCK8 as well as [111In]DOTA-MG0 specifically bound both CCK2R and CCK2i4svR with affinities in the low nanomolar range. In vivo experiments revealed that accumulation of both peptides in CCK2i4svR-positive tumours was similar (3.21 ± 0.77 and 3.01 ± 0.67%ID/g, sCCK8 and MG0, respectively, 24 h p.i.). Kidney retention of [111In]DOTA-MG0 (32.4 ± 7.5%ID/g, 24 h p.i.) was markedly higher than that of [111In]DOTA-sCCK8 (2.75 ± 0.31%ID/g, 24 h p.i.). We demonstrated that the CCK2i4svR is a potential target for PRRT using a radiolabelled sulfated CCK8 peptide. As this receptor is expressed on colorectal and pancreatic tumours, but not in normal tissue, these tumours are potentially new targets for PRRT with CCK8 and gastrin analogs. [ABSTRACT FROM AUTHOR]

The currently preferred radiopharmaceutical for positron emission tomography (PET) in oncology is 2-[[sup 18]F] fluoro-deoxyglucose (FDG). Increased accumulation of this deoxyglucose analogue in tumour cells is based on elevated glucose metabolism by tumour cells and subsequent trapping in the cells. In the search for new PET tracers, amino acids have been widely studied. A new amino acid tracer should preferably have similar high uptake in tumour cells but low non-specific uptake in normal tissues and any pathology other than tumour. In recent years, several amino acids have been labelled with either gamma radiation-emitting radionuclides or positron-emitting radionuclides, the most commonly used being carbon-11. However, the longer half-life of fluorine-18 matches better with the relatively slow process of protein synthesis and also facilitates shipping of the radiolabelled amino acids to hospitals without an onsite cyclotron or dedicated radiochemistry laboratory. The number of fluorinated amino acids under investigation is increasing, and one of the major points of discussion is the underlying mechanism of the tumour visualisation. While it has been shown that some amino acids can be used to measure the protein synthesis rate, others are used with the sole aim of measuring the rate of uptake into the cell. The differences between measuring amino acid transport (rate) and protein synthesis rate with [sup 18]F-labelled amino acids are discussed. [ABSTRACT FROM AUTHOR]

A correction to the article "Correlation of [18F]FMISO autoradiography and pimonidazole immunohistochemistry in human head and neck carcinoma xenografts," by Esther G.C. Troost and colleagues, in a 2008 issue.