Stabilization of neurotensin analogues:: effect on peptide catabolism, biodistribution and tumor binding

被引：61

作者：

Bruehlmeier, M ^{[1
]}

Garayoa, EG

Blanc, A

Holzer, B

Gergely, S

Tourwé, D

Schubiger, PA

Bläuenstein, P

机构：

[1] Paul Scherrer Inst, Ctr Radiopharmaceut Sci, CH-5232 Villigen, Switzerland

[2] Free Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium

来源：

NUCLEAR MEDICINE AND BIOLOGY | 2002年 / 29卷 / 03期

关键词：

tumor targeting; radiolabeled neurotensins; stabilization; biodistribution; tumor uptake;

D O I：

10.1016/S0969-8051(01)00304-3

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising, targets for imaging and therapeutic Purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [Tc-99m] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (NalphaHis)Ac-the Tc-binding moiety-combined with a reduced bond 8-9 (CH2NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：321 / 327

页数：7

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