Evaluation of arginine deiminase treatment in melanoma xenografts using 18F-FLT PET Journal Article


Authors: Stelter, L.; Fuchs, S.; Jungbluth, A. A.; Ritter, G.; Longo, V. A.; Zanzonico, P.; Raschzok, N.; Sauer, I. M.; Bomalaski, J. S.; Larson, S. M.
Article Title: Evaluation of arginine deiminase treatment in melanoma xenografts using 18F-FLT PET
Abstract: Purpose: This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3′-[18F]fluoro-3′-deoxythymidine ([ 18F]-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 18F-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 18F-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. © 2013 World Molecular Imaging Society.
Keywords: response evaluation; arginine deiminase; flt pet; melanoma xenograft
Journal Title: Molecular Imaging and Biology
Volume: 15
Issue: 6
ISSN: 1536-1632
Publisher: Springer  
Date Published: 2013-12-01
Start Page: 768
End Page: 775
Language: English
DOI: 10.1007/s11307-013-0655-6
PROVIDER: scopus
PUBMED: 23722880
PMCID: PMC4537614
DOI/URL:
Notes: Export Date: 2 January 2014 -- CODEN: CPIMF -- Source: Scopus
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MSK Authors
  1. Pat B Zanzonico
    355 Zanzonico
  2. Achim Jungbluth
    454 Jungbluth
  3. Gerd Ritter
    166 Ritter
  4. Steven M Larson
    958 Larson
  5. Valerie Ann Longo
    37 Longo