O super(6)-3-[ super(131)I]iodobenzylguanine: Improved Synthesis and Further Evaluation of a Potential Agent for Imaging of Alkylguanine-DNA Alkyltransferase

• Published in: Bioconjugate chemistry 2004-03, Vol.15 (2), p.402-408
• Main Authors: Vaidyanathan, G, Affleck, D J, Norman, J, Welsh, P, Liu, W, Johnson, S P, Friedman, H S, Zalutsky, M R
• Format: Article
• Language: English
• ISSN: 1043-1802
• DOI: 10.1021/bc0341977

O super(6)-Benzylguanine derivatives with suitable radionuclides attached to the benzyl ring are potentially useful in the noninvasive imaging of the DNA repair protein, alkylguanine-DNA alkyltransferase (AGT). Previously, O super(6)-3-[ super(131)I]iodobenzylguanine ([ super(131)I]IBG) was prepared using a two-step approach; we now report its synthesis in a single step by the radioiododestannylation of O super(6)-3-(trimethylstannyl)benzylguanine in 85-95% radiochemical yield. The in vitro specific uptake of [ super(131)I]IBG in DAOY human medulloblastoma cells, in TE-671 human rhabdomyosarcoma cells and a CHO cell line transfected to express AGT was linear (r super(2) = 0.9-1.0) as a function of cell density. After intravenous injection of [ super(131)I]IBG in athymic mice bearing TE-671 xenografts, tumor uptake was 1.38 plus or minus 0.34% ID/g at 0.5 h and declined at 2 and 4 h. Preadministration of O super(6)-(3-iodobenzyl) guanine (IBG) at 0.5 h increased uptake not only in tumor but also in several normal tissues. Notable exceptions were thyroid (p < 0.05), lung (p