True tracers: Comparing FDG with glucose and FLT with thymidine

As PET metabolic imaging becomes routine in clinical practice, there is a tendency to make imaging and data analysis fast and simple, but interpretation of these pictures by visual inspection does not do justice to the power of PET technology. Tissue data and blood data can be analyzed mathematically to provide parametric images of the PET tracer's biochemistry in terms of a transport parameter and a metabolic flux. The methods for parametric imaging with ¹¹C tracers of glucose and thymidine have been validated, but the short half-life of this radionuclide and the rapid metabolism of these labeled substrates to [¹¹C]CO₂ have led investigators to develop ¹⁸F analogs. While ¹⁸F substitution at critical positions in the natural substrate can block metabolism, it has other effects on the transport and metabolism of the analog tracer. The fidelity with which analog tracers mimic tracers of the authentic substrate is critically evaluated for [¹⁸F]-2-fluoro-2-deoxyglucose and [¹⁸F]-3′-fluoro- 3′-deoxythymidine.