Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using super(18)F-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'-[ super(18)F]fluoro-3'-deoxythy midine ([ super(18)F]-FLT) positron emission tomography (PET). Procedures: F-FLT response to ADI th...
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Veröffentlicht in: | Molecular imaging and biology 2013-12, Vol.15 (6), p.768-775 |
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Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Purpose: This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3'-[ super(18)F]fluoro-3'-deoxythy midine ([ super(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 super(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 super(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. |
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ISSN: | 1536-1632 1860-2002 |
DOI: | 10.1007/s11307-013-0655-6 |