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Evaluation of arginine deiminase treatment in melanoma xenografts using (18)F-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'-[(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.

journal_name

Mol Imaging Biol

journal_title

Molecular imaging and biology

authors

Stelter L,Fuchs S,Jungbluth AA,Ritter G,Longo VA,Zanzonico P,Raschzok N,Sauer IM,Bomalaski JS,Larson SM

doi

10.1007/s11307-013-0655-6

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

768-75

issue

6

eissn

1536-1632

issn

1860-2002

journal_volume

15

pub_type

杂志文章

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