2-[11C]Thymidine Positron Emission Tomography as an Indicator of Thymidylate Synthase Inhibition in Patients Treated With AG337

Background: Some anticancer drugs inhibit thymidylate syn-thase (TS), a key enzyme for thymidine nucleotide biosyn-thesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans. Methods: Five patients with advanced gas-trointestinal cancer were PET scanned both before and 1 hour after oral administration of the TS inhibitor AG337 (THYMITAQ [nolatrexed]); seven control patients were scanned twice but not treated with AG337. Thymidine sal-vage kinetics were measured in vivo using 2-[11C]thymidine PET and spectral analysis to obtain the standardized uptake values (SUV), the area under the time–activity curve (AUC), and the fractional retention of thymidine (FRT). Changes i