Preclinical evaluation of radiolabeled DOTA-derivatized cyclic minigastrin analogs for targeting cholecystokinin receptor expressing malignancies.
SourceMolecular Imaging and Biology, 14, 3, (2012), pp. 366-375
1 juni 2012
Article / Letter to editor
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Molecular Imaging and Biology
SubjectONCOL 3: Translational research NCMLS 2: Immune Regulation
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 (111)In and (68)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. (111)In-labeled cyclic DOTA-peptides showed a specific tumor uptake of ~1% ID/g in vivo, (68)Ga-labeled analogs of ~3% ID/g. Small animal SPECT imaging resulted to be superior with (111)In-DOTA-cyclo-MG2 in comparison with (111)In-DOTA-cyclo-MG1. CONCLUSIONS: Cyclic DOTA-minigastrin analogs are promising candidates for gastrin receptor scintigraphy and targeted radionuclide therapy.
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