An In-Depth Analysis of Alovudine F-18 ([18F]FLT) as a Radiopharmaceutical for Oncologic Imaging

Executive Summary

Alovudine F-18, more commonly known in the scientific literature as 3'-deoxy-3'-[$^{18}$F]fluorothymidine or [$^{18}$F]FLT, is an investigational small molecule radiopharmaceutical designed for the non-invasive imaging of cellular proliferation using Positron Emission Tomography (PET). As an isotopologue of the antiviral drug alovudine, its developmental history is bifurcated, originating from a therapeutic agent whose clinical progression was halted due to significant toxicity. However, when administered at tracer-level doses for diagnostic imaging, [$^{18}$F]FLT exhibits an excellent safety profile, a critical distinction that underpins its modern application.

The primary mechanism of [$^{18}$F]FLT involves its active transport into cells and subsequent phosphorylation by thymidine kinase 1 (TK1), an enzyme whose expression is tightly regulated and significantly upregulated during the S-phase of the cell cycle. This enzymatic trapping leads to the accumulation of the radiotracer in proliferating tissues, providing a quantitative surrogate for the rate of DNA synthesis via the salvage pathway. Unlike its metabolic counterpart, 2-deoxy-2-[$^{18}$F]fluoro-D-glucose ([$^{18}$F]FDG), which measures glucose metabolism, [$^{18}$F]FLT offers a more direct and specific assessment of tumor proliferation, a fundamental hallmark of cancer. This specificity allows it to better distinguish malignant tissue from sites of inflammation or infection, a significant limitation of [$^{18}$F]FDG.