Radiolabeled guanine derivatives for the in vivo mapping of O(6)-alkylguanine-DNA alkyltransferase: 6-(4-[(18)F]Fluoro-benzyloxy)-9H-purin-2-ylamine and 6-(3-[(131)I]Iodo-benzyloxy)-9H-purin-2-ylamine

Bioconjug Chem. 2000 Nov-Dec;11(6):868-75. doi: 10.1021/bc0000435.


Two radiolabeled analogues of 6-benzyloxy-9H-purin-2-ylamine (O(6)-benzylguanine; BG) potentially useful in the in vivo mapping of O(6)-alkylguanine-DNA alkyltransferase (AGT) were synthesized. Fluorine-18 labeling of the known 6-(4-fluoro-benzyloxy)-9H-purin-2-ylamine (FBG; 6) was accomplished by the condensation of 4-[(18)F]fluorobenzyl alcohol with 2-aminopurin-6-yltrimethylammonium chloride (4) or 2-amino-6-chloropurine in average decay-corrected radiochemical yields of 40 and 25%, respectively. Unlabeled 6-(3-iodo-benzyloxy)-9H-purin-2-ylamine (IBG; 7) was prepared from 4 and 3-iodobenzyl alcohol. Radioiodination of 9, prepared from 7 in two steps, and subsequent deprotection gave [(131)I]7 in about 70% overall radiochemical yield. The IC(50) values for the inactivation of AGT from CHO cells transfected with pCMV-AGT were 15 nM for IBG and 50 nM for FBG. The binding of [(18)F]6 and [(131)I]7 to purified AGT was specific and saturable with both exhibiting similar IC(50) values (5-6 microM).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Magnetic Resonance Spectroscopy
  • O(6)-Methylguanine-DNA Methyltransferase / antagonists & inhibitors
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism*
  • Purines / chemistry
  • Purines / metabolism*
  • Spectrometry, Mass, Fast Atom Bombardment


  • 6-(3-iodo-benzyloxy)-9H-purin-2-ylamine
  • 6-(4-(18)fluoro-benzyloxy)-9H-purin-2-ylamine
  • Purines
  • O(6)-Methylguanine-DNA Methyltransferase