[(99m)Tc]Demomedin C, a radioligand based on human gastrin releasing peptide(18-27): synthesis and preclinical evaluation in gastrin releasing peptide receptor-expressing models

Nock, Berthold A; Cescato, Renzo; Ketani, Eleni; Waser, Beatrice; Reubi, Jean Claude; Maina, Theodosia (2012). [(99m)Tc]Demomedin C, a radioligand based on human gastrin releasing peptide(18-27): synthesis and preclinical evaluation in gastrin releasing peptide receptor-expressing models. Journal of medicinal chemistry, 55(19), pp. 8364-74. Easton, Pa.: American Chemical Society 10.1021/jm300741f

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The synthesis and preclinical evaluation of [(99m)Tc]Demomedin C in GRPR-expressing models are reported. Demomedin C resulted by coupling a Boc-protected N(4)-chelator to neuromedin C (human GRP(18-27)), which, after (99m)Tc-labeling, afforded [(99m)Tc]Demomedin C. Demomedin C showed high affinity and selectivity for the GRPR during receptor autoradiography on human cancer samples (IC(50) in nM: GRPR, 1.4 ± 0.2; NMBR, 106 ± 18; and BB(3)R, >1000). It triggered GRPR internalization in HEK-GRPR cells and Ca(2+) release in PC-3 cells (EC(50) = 1.3 nM). [(99m)Tc]Demomedin C rapidly and specifically internalized at 37 °C in PC-3 cells and was stable in mouse plasma. [(99m)Tc]Demomedin C efficiently and specifically localized in human PC-3 implants in mice (9.84 ± 0.81%ID/g at 1 h pi; 6.36 ± 0.85%ID/g at 4 h pi, and 0.41 ± 0.07%ID/g at 4 h pi block). Thus, human GRP-based radioligands, such as [(99m)Tc]Demomedin C, can successfully target GRPR-expressing human tumors in vivo while displaying attractive biological features--e.g. higher GRPR-selectivity--vs their frog-homologues.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Cescato, Renzo and Reubi, Jean-Claude

ISSN:

0022-2623

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:32

Last Modified:

17 Mar 2015 21:20

Publisher DOI:

10.1021/jm300741f

PubMed ID:

22966957

Web of Science ID:

000309643500015

URI:

https://boris.unibe.ch/id/eprint/12487 (FactScience: 218839)

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