title: Preclinical evaluation of 68Ga-DOTA-minigastrin for the detection of cholecystokinin-2/gastrin receptor-positive tumors.
abstract: In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor-mediated uptake (p  =  .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.
authors: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.brom@nucmed.umcn.nl
authors: Maarten
authors: M
authors: Brom
authors: Lieke
authors: L
authors: Joosten
authors: Peter
authors: P
authors: Laverman
authors: Wim J G
authors: WJ
authors: Oyen
authors: Martin
authors: M
authors: Béhé
authors: Martin
authors: M
authors: Gotthardt
authors: Otto C
authors: OC
authors: Boerman
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002766:Cholecystokinin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D056831:Coordination Complexes; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005755:Gastrins; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats; D043887:Receptor, Cholecystokinin B / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000000981:diagnostic imaging / Q000473:pathology; D014018:Tissue Distribution
chemical_list: C561740:68Ga-DOTA-minigastrin; D056831:Coordination Complexes; D005755:Gastrins; D043887:Receptor, Cholecystokinin B; C008530:minigastrin; D002766:Cholecystokinin