Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using 18F-FLT PET

Purpose This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]-FLT) positron emission tomography (PET). Procedures F-FLT response to ADI therapy was studied in preclinical models of melanoma in vitro and in vivo . The molecular mechanism of response to ADI therapy was investigated, with a particular emphasis on biological pathways known to regulate 18 F-FLT metabolism. Results Proliferation of SK-MEL-28 melanoma tumors was potently inhibited by ADI treatment. However, no metabolic response was observed in FLT PET, presumably based on the known ADI-induced degradation of PTEN, followed by instability of the tumor suppressor p53 and a relative overexpression of thymidine kinase 1, the enzyme mainly responsible for intracellular FLT processing. Conclusion The specific pharmacological properties of ADI preclude using 18 F-FLT to evaluate clinical response in melanoma and argue for further studies to explore the use of other clinically applicable PET tracers in ADI treatment.