Development of the First ¹⁸F-Labeled Radiohybrid-Based Minigastrin Derivative with High Target Affinity and Tumor Accumulation by Substitution of the Chelating Moiety.

ABSTRACT: In order to optimize elevated kidney retention of previously reported minigastrin derivatives, we substituted (R)-DOTAGA by DOTA in (R)-DOTAGA-rhCCK-16/-18. CCK-2R-mediated internalization and affinity of the new compounds were determined using AR42J cells. Biodistribution and µSPECT/CT imaging studies at 1 and 24 h p.i. were carried out in AR42J tumor-bearing CB17-SCID mice. Both DOTA-containing minigastrin analogs exhibited 3- to 5-fold better IC₅₀ values than their (R)-DOTAGA-counterparts. ^natLu-labeled peptides revealed higher CCK-2R affinity than their ^natGa-labeled analogs. In vivo, tumor uptake at 24 h p.i. of the most affine compound, [¹⁹F]F-[¹⁷⁷Lu]Lu-DOTA-rhCCK-18, was 1.5- and 13-fold higher

SUBMITTER: Gunther T 

PROVIDER: S-EPMC10054553 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature