Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc

Nock, Berthold A; Nikolopoulou, Anastasia; Reubi, Jean-Claude; Maes, Veronique; Conrath, Peter; Tourwé, Dirk; Maina, Theodosia (2006). Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc. Journal of medicinal chemistry, 49(15), pp. 4767-76. Easton, Pa.: American Chemical Society 10.1021/jm060415g

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A series of Gly-neurotensin(8-13) analogues modified at the N-terminus by acyclic tetraamines (Demotensin 1-4) were obtained by solid-phase peptide synthesis techniques. Strategic replacement of amino acids and/or reduction of sensitive peptide bonds were performed to enhance conjugate resistance against proteolytic enzymes. During 99mTc-labeling, single species radiopeptides, [99mTc]Demotensin 1-4, were easily obtained in high yields and typical specific activities of 1 Ci/micromol. Peptide conjugates displayed a high affinity binding to the human neurotensin subtype 1 receptor (NTS1-R) expressed in colon adenocarcinoma HT-29 or WiDr cells and/or in human tumor sections. [99mTc]Demotensin 1-4 internalized very rapidly in HT-29 or WiDr cells by a NTS1-R-mediated process. [99mTc]Demotensin 3 and 4, which remained stable during 1 h incubation in murine plasma, were selectively studied in nude mice bearing human HT-29 and WiDr xenografts. After injection, [99mTc]Demotensin 3 and 4 effectively and specifically localized in the experimental tumors and were rapidly excreted via the kidneys into the urine, exhibiting overall biodistribution patterns favorable for NTS1-R-targeted tumor imaging in man.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Reubi-Kattenbusch, Jean-Claude
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	0022-2623
ISBN:	16854083
Publisher:	American Chemical Society
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:48
Last Modified:	05 Dec 2022 14:15
Publisher DOI:	10.1021/jm060415g
PubMed ID:	16854083
Web of Science ID:	000239141500036
URI:	https://boris.unibe.ch/id/eprint/20295 (FactScience: 3551)