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
Hauptverfasser: Stelter, Lars, Fuchs, Simon, Jungbluth, Achim A, Ritter, Gerd, Longo, Valerie A, Zanzonico, Pat, Raschzok, Nathanael, Sauer, Igor M, Bomalaski, John S, Larson, Steven M
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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.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-013-0655-6