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Open Access Green as soon as Postprint is submitted to ZB.
[18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner.
Eur. J. Nucl. Med. Mol. Imaging 40, 34-43 (2012)
PURPOSE: Positron emission tomography (PET) with the thymidine analogue [(18)F]fluorothymidine ([(18)F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [(18)F]FLT to the glucose analogue [(18)F]fluorodeoxyglucose ([(18)F]FDG) regarding dose-dependent visualization and prediction of early therapy response. METHODS: Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [(18)F]FLT and [(18)F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [(18)F]FLT and [(18)F]FDG uptake 48 h later. RESULTS: In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 μg to 200 μg. The mean tumour-to-background ratio (TBR) of [(18)F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [(18)F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [(18)F]FLT uptake, in contrast to a variable and decelerated reduction in [(18)F]FDG uptake. Thus, the increase in [(18)F]FDG uptake in vivo presumably reflected nonspecific glucose metabolism of inflammatory cells, as confirmed by histology of explanted lymphomas. CONCLUSION: Early responses to dose-dependent antiproliferative treatment in high-grade lymphoma are more accurately visualized with [(18)F]FLT PET than with [(18)F]FDG PET.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
FLT PET; FDG PET; Lymphoma; Dose-dependency; Therapy monitoring; Non-hodgkins-lymphoma ; Positron-emission-tomography ; B-cell Lymphoma ; Imaging Proliferation ; F-18-flt Uptake ; In-vitro ; Fdg-pet ; Cancer ; Tumor ; Chemotherapy
Language
english
Publication Year
2012
HGF-reported in Year
2012
ISSN (print) / ISBN
1619-7070
e-ISSN
1432-105X
Quellenangaben
Volume: 40,
Issue: 1,
Pages: 34-43
Publisher
Springer
Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500390-001
G-500300-001
G-500300-001
PubMed ID
23053327
WOS ID
WOS:000312082500006
Erfassungsdatum
2012-11-20