Background: Developed as an antiviral drug in the 1960s and 1970s, the
thymidine analogue 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU)
was translated to clinical application for treatment of herpes simplex virus infection. In
phase I clinical trial of FMAU; however, patients experienced neurotoxicity at the pharmacological
dose, and FMAU was withdrawn from the trial. More recently, FMAU has
been developed as a tracer for positron emission tomography (PET) imaging in early detection
of cancer through its binding to human thymidine kinase, which is upregulated in
cancer cells. FMAU radiolabeled with 11C or 18F has been examined for PET imaging of
tumor cell proliferation and DNA synthesis. Although many reports have been partially
published on FMAU, systematic reviews outlining the historic development and imaging
probe are lacking. This review is focused on the identification of kinases, the chemistry of
FAMU and its application in cancer diagnosis and therapy assessment.
Objective: The aim of this study was to review the historic development of FMAU, from
its synthetic development and antiviral activity studies to its radiolabeling and evaluate it
as a PET imaging probe for the early detection of cancer and assessment of treatment response,
including published reports on the clinical utility of 18F-FMAU.
Conclusion: While FMAU was not successful as an antiviral agent, 18F-FMAU is a suitable
radiotracer for early detection of cancer and assessment of response to therapy by
PET. The process of clinical grade 18F-FMAU production requires further improvement.
18F-FMAU has high potential for clinical application, but further extensive studies are
needed to establish this tracer in the diagnosis of various cancers and assessment of their
response to therapy.