Is 3'-deoxy-3'- [18F] fluorothymidine ([18F]-FLT) the next tracer for routine clinical PET after R [18F]-FDG?

Abstract

Positron emission tomography (PET) with [18F]-FDG is now firmly established as a clinical tool in oncology. Its applications are however limited in some indications, due to the lack of specificity of its uptake mechanism for tumors, or the low avidity of some cancer types such as prostate. Alternative tracers are thus being developed, in order to fill up this void. Proliferation as a biological target is particularly attractive in cancer imaging. From that perspective, fluorothymidine ([18F]-FLT or FLT) has generated a strong interest among the scientific community, especially since the radiosynthesis process has been improved and simplified, thus making possible to envision a routine use for the tracer. This article aims at summarizing the status of the current scientific data regarding FLT. The uptake mechanism of FLT is well known, relying on the thymidine kinase 1 (TK1) enzymatic activity, and thus on DNA synthesis. Preclinical studies have shown a clear relationship between tracer accumulation and level of tumor proliferation, even though DNA salvage pathwayss intervene in the process and may complicate the interpretation of the results. Several clinical studies suggest a good specificity for tumor, albeit with a lower sensitivity than with FDG. In all likelihood however, the future of FLT lies in the evaluation of antitumor response and possibly the pretherapeutic prognostic characterization, rather than in the diagnosis and staging of malignancies. Although the scientific data regarding this issue remain limited, initial results are encouraging. Further significant work remains to be done in order to fully assess the clinical performances of the tracer, on the one hand, and to determine its place relative to FDG and other emerging tracers, on the other hand. Until these studies are completed, FLT should be considered as a promising tracer, but remaining at an experimental stage of its development