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

被引：2

作者：

Mukai, Takahiro ^{[1
]}

Taketomi, Masato ^{[1
]}

Tashiro, Masaaki ^{[1
]}

Yamamoto, Fumihiko ^{[1
]}

Maeda, Minoru ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Pharmaceut Sci, Higashi Ku, Fukuoka 8128582, Japan

来源：

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS | 2009年 / 52卷 / 5-6期

关键词：

thymidine phosphorylase; tumor; radiolabeled inhibitor; 6-METHYLENE-BRIDGED URACIL DERIVATIVES; CELL-GROWTH-FACTOR; SOLID TUMORS; URIDINE PHOSPHORYLASE; ANGIOGENIC ENZYME; EXPRESSION; INHIBITORS; CARCINOMA; TAS-102; ADENOCARCINOMA;

D O I：

10.1002/jlcr.1581

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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-[I-125] iodouracil ([I-125]1) as a TP-targeted radiopharmaceutical. No-carrier-added [I-125]1 was synthesized by halogen exchange of the corresponding bromide (2). After purification by reverse-phase HPLC, [I-125]1 showed a radiochemical purity of over 97%. When administered to normal mice, [I-125], 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 [I-125]1. These findings suggest that [I-125]1 possesses the required properties for in vivo imaging of TIP activity.

引用

页码：146 / 150

页数：5

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