6533b851fe1ef96bd12aa20d
RESEARCH PRODUCT
An approach to the evaluation of the activity of the DNA repair enzyme O6-methylguanine-DNA-methyl-transferase in tumor tissue in vivo: syntheses of 6-benzyloxy-9-(2-[18F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[18F]fluoroethyl)-7H-purin-2-yl-amine
Esther NesselerBernd KainaMathias SchreckenbergerFrank RöschUta EichhornRalf SchirrmacherWilhelm Hamkenssubject
MaleAlkylating AgentsFluorine RadioisotopesBiodistributionDNA RepairDNA repairStereochemistryDrug ResistanceMice NudeMiceO(6)-Methylguanine-DNA MethyltransferaseIn vivoDNA Repair ProteinAnimalsHumansTissue DistributionEnzyme InhibitorsFluoroethylRadiationChemistryNeoplasms ExperimentalIn vitroPurinesAmine gas treatingHeLa CellsAlkyltransferasedescription
Abstract The resistance of tumor cells to the cytostatic activity of methylating and chloroethylating anticancer drugs is determined by the level of expression of the DNA repair protein O 6 -methylguanine-DNA-methyl-transferase (MGMT). The synthesis of labelled 6-benzyloxy-9H-purin-2-ylamine derivatives should hence allow a quantification of the MGMT status of tumor and non-target tissue in vivo. 6-benzyloxy-9-(2-fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-fluoroethyl)-7H-purin-2-yl-amine were synthesized and evaluated in vitro, both showing an affinity of 1.8 μM. 6-benzyloxy-9-(2-[ 18 F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[ 18 F]fluoroethyl)-7H-purin-2-yl-amine were synthesized by alkylation of 6-benzyloxy-9H-purin-2-ylamine with 1-[ 18 F]fluoro-2-tosylethane in optimized yields of 41% and 20%, respectively. Biodistribution studies were performed in nude mice, carrying mex+ (MGMT expressing) and mex− tumors.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2002-04-02 | Applied Radiation and Isotopes |