Evaluation of 62Cu labeled diacetyl-bis(N4-methoylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer

Cu-62 labeled diacetyl-bis(N-4-methylthiosemicarbazone) (Cu-62-ATSM) has been proposed as a generator-produced, positron-emitting tracer for hypoxic tissue imaging. From basic studies, the retention mechanism of Cu-62-ATSM is considered to be closely related to cytosolic/microsomal bioreduction, a possible system for hypoxic bioreductive drug activation. In order to evaluate the characteristics of Cu-62-ATSM, PET studies were performed in 4 normal subjects and 6 patients with lung cancer. Cu-62-ATSM cleared rapidly from the blood with little lung uptake (0.43 +/- 0.09, uptake ratio; divided by the arterial input function) in normal subjects. Intense tumor uptake of Cu-62-ATSM was observed in all patients with lung cancer (3.00 +/- 1.50). A negative correlation was observed between blood flow and flow-normalized Cu-62-ATSM uptake in three of four patients. In contrast, Cu-62-ATSM uptake was not related to that of F-18-fluorodeoxyglucose. The negative correlation between blood flow and flow normalized Cu-62-ATSM uptake suggests an enhancement of retention of Cu-62-ATSM by low flow. Cu-62-ATSM is a promising FET tracer for tumor imaging, which might bring new information for chemotherapeutic treatment as well as radiotherapy of hypoxic tumors.