Synthesis and characterization of αvβ3-targeting peptidomimetic chelate conjugates for PET and SPECT imaging

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Kim, Young-Seung¹  Nwe, Kido¹  Milenic, Diane E.¹  Brechbiel, Martin W.¹  Satz, Stanley²  Baidoo, Kwamena E.¹ 

[1] NCI, Radioimmune & Inorgan Chem Sect, ROB, NIH, Bethesda, MD 20892 USA

[2] Adv Imaging Projects Inc, Doral, FL USA

关键词: Integrin alpha(v)beta(3);    NODAGA;    DOTAGA;    Peptidomimetics;    Antagonist;    Ga-68;    Pb-203;    PET imaging;    SPECT imaging;   

DOI  :  10.1016/j.bmcl.2012.07.024

来源: Elsevier

【 摘 要 】

There is growing interest in small peptidomimetic alpha(v)beta(3) integrin antagonists that are readily synthesized and characterized and can be easily handled using physiological conditions. Peptidomimetic 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1-carbamyl)] -aminoethylsulfonyl-amino-beta-alanine (IAC) was successfully conjugated to 1-(1-carboxy-3-carbo-t-but-oxypropyl)-4,7-(carbo-tert-butoxymethyl)-1,4,7-triazacyclononane (NODA-GA(tBu)(3)) and 1-(1-carboxy-3-carbotertbutoxymethyl)-1,4,7,10-tetraazacyclododecane (DOTA-GA(tBu)(4)) and radiolabeled with In-111, Ga-67 and Pb-203. Results of a radioimmunoassay demonstrated binding to purified alpha(v)beta(3) integrin when 14 equiv of integrin were added to the reaction. Based on this promising result, investigations are moving forward to evaluate the NODA-GA-IAC and DOTA-GA-IAC conjugates for targeting tumor associated angiogenesis and alpha(v)beta(3) integrin positive tumors to define their PET and SPECT imaging qualities as well as their potential for delivery of therapeutic radionuclides. Published by Elsevier Ltd.

【 授权许可】

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