Document Detail


FLT-PET Is Superior to FDG-PET for Very Early Response Prediction in NPM-ALK-Positive Lymphoma Treated with Targeted Therapy.
MedLine Citation:
PMID:  22875026     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The prognosis of relapsed or refractory aggressive lymphoma is poor. The huge variety of currently evolving targeted treatment approaches would benefit from tools for early prediction of response or resistance. We used various ALK-positive anaplastic large cell lymphoma (ALCL) cell lines to evaluate two inhibitors, the HSP90 inhibitor NVP-AUY922, and the mTOR inhibitor everolimus, both of which have shown to interfere with ALK-dependent oncogenic signal transduction. Their therapeutic effect was determined in vitro by MTT assay, [18F]fluorodeoxyglucose- (FDG) and [18F]fluorothymidine- (FLT) uptake, and by biochemical analysis of ALK-induced signalling. Micro FDG- and FLT-PET imaging studies in immunodeficient mice bearing ALCL xenotransplants were performed with the cell lines SUDHL-1 and Karpas299 to assess early treatment response to NVP-AUY922 or everolimus in vivo. SUDHL-1 cells showed sensitivity to both inhibitors in vitro. Importantly, we detected a significant reduction of FLT-uptake in SUDHL-1 bearing animals using both inhibitors compared to baseline as early as 5 days after initiation of targeted therapy. Immunostaining showed a decrease in Ki-67 and an increase in cleaved caspase-3 staining. In contrast, FDG-uptake did not significantly decrease at early time points. Karpas299 xenotransplants, which are resistant to NVP-AUY922 and sensitive to everolimus treatment, showed an increase of mean FLT-uptake on day 2 after administration of NVP-AUY299, but a significant reduction in FLT-uptake upon everolimus treatment. In conclusion, we show that FLT- but not FDG-PET is able to predict response to treatment with specific inhibitors very early in the course of treatment and thus enables early prediction of treatment efficacy.
Authors:
Zhoulei Li; Nicolas A Graf; Ken Herrmann; Alexandra Jünger; Michaela Aichler; Annette Feuchtinger; Anja Baumgart; Axel Walch; Christian Peschel; Markus Schwaiger; Andreas Buck; Ulrich Keller; Tobias Dechow
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Nuclear Medicine, Technische Universität München.
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