New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with 68Ga3+

详细信息    查看全文

• 作者：Michelle T. Ma ; Carleen Cullinane ; Cinzia Imberti ; Julia Baguña Torres ; Samantha Y. A. Terry ; Peter Roselt ; Rodney J. Hicks ; Philip J. Blower
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：February 17, 2016
• 年：2016
• 卷：27
• 期：2
• 页码：309-318
• 全文大小：428K
• ISSN：1520-4812

文摘

Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with ⁶⁸Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by treatment with generator-produced ⁶⁸Ga³⁺ in over 95% radiochemical yield under ambient conditions in less than 5 min, with specific activities of 60–80 MBq nmol^–1. Competitive binding assays and in vivo biodistribution in mice bearing U87MG tumors demonstrate that the new ⁶⁸Ga³⁺-labeled THP peptide conjugates retain affinity for the α_vβ₃ integrin receptor, clear within 1–2 h from circulation, and undergo receptor-mediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of ⁶⁸Ga biomolecules under mild conditions suitable for peptides and proteins.