O6-3-[131I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

详细信息    查看全文

• 作者：Ganesan Vaidyanathan ; Donna J. Affleck ; Joseph Norman ; Phil Welsh ; Wenge Liu ; Stewart P. Johnson ; Henry S. Friedman ; and Michael R. Zalutsky
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：March 2004
• 年：2004
• 卷：15
• 期：2
• 页码：402 - 408
• 全文大小：110K
• 年卷期：v.15,no.2(March 2004)
• ISSN：1520-4812

文摘

O⁶-Benzylguanine derivatives with suitable radionuclides attached to the benzyl ring are potentiallyuseful in the noninvasive imaging of the DNA repair protein, alkylguanine-DNA alkyltransferase(AGT). Previously, O⁶-3-[¹³¹I]iodobenzylguanine ([¹³¹I]IBG) was prepared using a two-step approach;we now report its synthesis in a single step by the radioiododestannylation of O⁶-3-(trimethylstannyl)benzylguanine in 85-95% radiochemical yield. The in vitro specific uptake of [¹³¹I]IBG in DAOY humanmedulloblastoma cells, in TE-671 human rhabdomyosarcoma cells and a CHO cell line transfected toexpress AGT was linear (r² = 0.9-1.0) as a function of cell density. After intravenous injection of[¹³¹I]IBG in athymic mice bearing TE-671 xenografts, tumor uptake was 1.38 ± 0.34% ID/g at 0.5 hand declined at 2 and 4 h. Preadministration of O⁶-(3-iodobenzyl)guanine (IBG) at 0.5 h increaseduptake not only in tumor but also in several normal tissues. Notable exceptions were thyroid (p <0.05), lung (p <0.05) and stomach. After intratumoral injection of [¹³¹I]IBG in the same xenograftmodel, the uptake in tumors that were depleted of AGT by BG treatment (165.8 ± 27.5% ID/g) wasabout 60% of that in control mice (272.4 ± 48.2% ID/g; p < 0.05).