Radiosynthesis and Biodistribution of a Prosthetic Group (18F-FENMA) Conjugated to Cyclic RGD Peptides

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• 作者：Dag Erlend Olberg ; Alan Cuthbertson ; Magne Solbakken ; Joseph M. Arukwe ; Hong Qu ; Alexandr Kristian ; Skjalg Bruheim ; Ole Kristian Hjelstuen
• 刊名：Bioconjugate Chemistry
• 出版年：2010
• 出版时间：December 15, 2010
• 年：2010
• 卷：21
• 期：12
• 页码：2297-2304
• 全文大小：264K
• 年卷期：v.21,no.12(December 15, 2010)
• ISSN：1520-4812

文摘

We have recently reported a new N-methylaminooxy-based prosthetic group for the site-selective introduction of ¹⁸F-fluorine under mild acidic aqueous conditions into model peptides functionalized with a Michael acceptor moiety. To further investigate the utility of this methodology, the radiosynthesis of two cyclic RGD peptides was carried out, and in vivo biodistribution and microPET studies were performed in tumor-bearing mice. A cyclic RGD peptide was functionalized with the Michael acceptors trans-β-nitrostyrene carboxylic acid and 3-vinylsulfonylpropionic acid. Radiolabeling was then performed with the prosthetic group O-(2-(2-[¹⁸F]fluoroethoxy)ethyl)-N-methylhydroxylamine (¹⁸F-FENMA) yielding the ¹⁸F-conjugates in moderate yields (8.5−12%). Biodistribution, blocking, and microPET imaging studies were performed in a mouse xenograft model. The vinylsulfonyl-modified conjugate demonstrated good in vitro plasma stability. Biodistribution and microPET studies revealed excellent tumor uptake with low background in key organs and renal elimination as the predominant route of excretion. Blocking studies with coinjected nonlabeled RGD peptide confirmed the in vivo specificity for the integrin α_vβ₃. On the other hand, ¹⁸F-FENMA-nitrostyrene-RGD, although stable at conjugation pH 5, was found to rapidly degrade at physiological pH through loss of the ¹⁸F-prosthetic group.