title: Evaluation of arginine deiminase treatment in melanoma xenografts using (18)F-FLT PET.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Charité CVK-Universitätsmedizin Berlin, 13353, Berlin, Germany, lars.stelter@charite.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Stelter
authors.forename: Simon
authors.initials: S
authors.lastname: Fuchs
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Longo
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Nathanael
authors.initials: N
authors.lastname: Raschzok
authors.forename: Igor M
authors.initials: IM
authors.lastname: Sauer
authors.forename: John S
authors.initials: JS
authors.lastname: Bomalaski
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics*; D006867:Hydrolases / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D013937:Thymidine Kinase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D006867:Hydrolases; C019723:arginine deiminase; C002854:alovudine