In vivo and in vitro characterization of CCK8 bearing a histidine-based chelator labeled with Tc-99m-tricarbonyl(475 views) D'Andrea LD, Testa I, Panico M, Di Stasi R, Carac C, Tarallo L, Arra C, Barbieri A, Romanelli A, Aloj L
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Area Funzionale di Medicina Nucleare, Istituto Nazionale Tumori, Fondazione G. Pascale, Via M. Semmola, 80131 Napoli, Italy
UOS Sperimentazione Animale, Istituto Nazionale Tumori, Fondazione G. Pascale, 80131 Napoli, Italy
Dipartimento delle Scienze Biologiche, Università di Napoli Federico II, 80134 Napoli, Italy
References: Not available.
In vivo and in vitro characterization of CCK8 bearing a histidine-based chelator labeled with Tc-99m-tricarbonyl
The development of receptor targeting radiolabeled ligands has gained much interest in recent years for diagnostic and therapeutic applications in nuclear medicine. Cholecystokinin (CCK) receptors have been shown to be overexpressed in a subset of neuroendocrine and other tumors. We are evaluating binding and biodistribution properties of a CCK8 peptide derivative labeled with Tc-99m(I)-tricarbonyl. The CCK8 peptide was modified at its N-terminus by adding to its N-terminus two lysine-histidine modules (KH), where histidine is coupled to the side chain of the lysine ((KH)(2)-CCK8). Tc-99m(I)-tricarbonyl was generated with the IsoLink (TM) kit. A431 cells stably transfected with a cDNA encoding for the human CCK2 receptor were utilized to determine binding affinity, internalization, and retention of the labeled peptide, in comparison with wild-type A431 cells. A nude mouse tumor model was obtained by generating A431-CCK2R and A431-control tumors in opposite flanks of the animals. High specific activity labeling with 99(m)Tc was achieved. In A431-CCK2R cells, specific saturable binding was observed as well as evident internalization of the radiolabeled peptide after binding. Biodistribution experiments showed rapid, specific localization of (KH)(2)-CCK8 on A431-CCK2R xenografts compared with control tun-tors, although absolute uptake values were not markedly higher compared with background activity. Clearance of unbound radioactivity was both urinary and hepatobiliary. In imaging experiments, while targeting to CCK2R positive tumors could be appreciated, there was poor contrast between target and nontarget areas. (KH)2-CCK8 shows adequate in vitro and in vivo properties for CCK2R targeting although improvement of biodistribution warrant further development. (C) 2008 Wiley Periodicals, Inc.
In vivo and in vitro characterization of CCK8 bearing a histidine-based chelator labeled with Tc-99m-tricarbonyl
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(517 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote
Hesse B, Tagil K, Cuocolo A, Anagnostopoulos C, Bardies M, Bax J, Bengel F, Busemann Sokole E, Davies G, Dondi M, Edenbrandt L, Franken P, Kjaer A, Knuuti J, Lassmann M, Ljungberg M, Marcassa C, Marie PY, Mckiddie F, O'connor M, Prvuolovich E, Underwood R * 3. 0 T perfusion MR imaging(990 views) Rivista Di Neuroradiologia (ISSN: 1120-9976), 2004; 17(6): 807-812. Impact Factor:0.023 ViewExport to BibTeXExport to EndNote