Synthesis of 2-amino-6-(2-[18F]fluoro-pyridine-4-ylmethoxy)-9-(octyl-β-d-glucosyl)-purine: a novel radioligand for positron emission tomography studies of the O6-methylguanine-DNA methyltransferase (MGMT) status of tumour tissue

Abstract The synthesis of the novel glucose conjugated O6-methylguanine-DNA methyltransferase (MGMT) inhibitor 2-amino-6-(2-[18F]fluoro-pyridine-4-ylmethoxy)-9-(octyl-α- d -glucosyl)-purine is reported. This compound might serve as a radiotracer for the determination of the MGMT status of tumour tissue.

ChemInform Abstract: Synthesis of 2-Amino-6-(2- [18F] fluoro-pyridine-4-ylmethoxy)-9-(octyl-β-D-glucosyl)-purine: A Novel Radioligand for Positron Emission Tomography Studies of the O6-Methylguanine-DNA Methyltransferase (MGMT) Status of Tumor Tissue.

Inactivation of O(6)-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors.

The DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a decisive determinant of resistance of tumor cells to methylating and chloroethylating anti-cancer drugs. Therefore, selective inhibition of MGMT in tumors is expected to cause tumor sensitization. Several inhibitors of MGMT have been developed which function in both tumors and normal tissue. To deplete MGMT preferentially in tumors, strategies to target the inhibitor to the tumor tissue need to be developed. Here, we report on the properties of glucose-conjugated MGMT inhibitors that might be useful for tumor targeting since tumor cells frequently over-express glucose transporter. O6-Benzylguanine (O6BG), 8-aza-O6-ben…