Tumor Diagnosis with New In-111-Radioligands Based on Truncated Human Gastrin Releasing Peptide Sequences: Synthesis and Preclinical Comparison

Pantelis Marsouvanidis, T Maina, W Sallegger, Eric Krenning, Marion Jong, Berthold Nock

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10 Citations (Scopus)


Radiolabeled analogs of the frog tetradecapeptide bombesin (BBN) have been proposed for diagnosis and therapy of gastrin releasing peptide receptor (GRPR)-expressing tumors. Following a different and yet unexplored approach, we have developed four novel In-111-labeled truncated analogs of the human 27-mer GRP after conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) at the N-terminus of GRP(13/14/17/18-27) fragments. Analog affinities for the human GRPR determined against [I-125-Tyr(4)]BBN were at the nanomolar level and dependent on truncation site. The respective In-111 radioligands specifically internalized in GRPR-expressing PC-3 cells. The shorter chain [In-111-DOTA]GRP(17/18-27) analogs showed higher stability in mice. Radioligands specifically localized in human PC-3 xenografts in SCID mice, with [In-111-DOTA]GRP(17-27) exhibiting the most favorable pharmacokinetic profile. This study has demonstrated the efficacy of human GRP-based radiopeptides to target GRPR-positive lesions in vivo and has revealed the impact of GRP chain length on key biological parameters of resulting radiotracers.
Original languageUndefined/Unknown
Pages (from-to)8579-8587
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number21
Publication statusPublished - 2013

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