6‐[(2‐Iminopyrrolidinyl)methyl]‐5‐[125I]iodouracil as a potential thymidine phosphorylase‐targeted radiopharmaceutical: synthesis and preliminary biological evaluation

Thymidine phosphorylase (TP) is expressed at higher levels in many types of malignant tumors than in adjacent nonneoplastic tissues. The aim of this study was to develop a radiolabeled TP inhibitor, 6‐[(2‐iminopyrrolidinyl)methyl]‐5‐[¹²⁵I]iodouracil ([¹²⁵I]1) as a TP‐targeted radiopharmaceutical. No‐carrier‐added [¹²⁵I]1 was synthesized by halogen exchange of the corresponding bromide (2). After purification by reverse‐phase HPLC, [¹²⁵I]1 showed a radiochemical purity of over 97%. When administered to normal mice, [¹²⁵I]1 showed a rapid clearance from the blood and a low accumulation in the thyroid and stomach, indicating good in vivo stability against deiodination. By coinjection of unlabeled 1, the uptakes in the TP‐expressing normal tissues, small intestine and liver were significantly reduced, suggesting TP‐specific modes of accumulation of [¹²⁵I]1. These findings suggest that [¹²⁵I]1 possesses the required properties for in vivo imaging of TP activity. Copyright © 2009 John Wiley & Sons, Ltd.