In Vitro and In Vivo Characterization of Three ~(68)Ga- and~(111)In-Labeled Peptides for Cholecystokinin Receptor Imaging

摘要

Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK_2 receptor (CCK_2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe~2(p-CH_2SO_3H), Nle_36], are suitable for imaging of CCK_2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK_2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe~2(p-CH_2SO_3H), Nle~(3,6)], and DOTA-MG0, labeled with ~(111)ln or ~(68)Ga, was evaluated in BALB/c nude mice with a subcutaneous A4_31-CCK_2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK_2R-expressing tumors. Both ~(111)ln-DOTA-sCCK8 and ~(111)ln-DOTA-sCCK8[Phe~2(p-CH_2SO_3H), Nle~(3,6)] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A4_31-CCK_2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK_2R-positive tumors.