RT Journal Article
SR Electronic
T1 Enhanced 18F-FLT uptake in tumor xenografts after mild FdUrd pretreatment
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1560
OP 1560
VO 50
IS supplement 2
A1 David Viertl
A1 Angelika Bischof Delaloye
A1 Simon Ametamey
A1 Tobias Ross
A1 Florence Perillo
A1 Marek Kosinski
A1 Yves  Dupertuis
A1 Franz Buchegger
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1560.abstract
AB 1560 Objectives 18F-fluorothymidine (FLT) is a PET proliferation tracer. However, FLT tumor uptake may be low compared with FDG. We evaluated preconditioning of tumor-bearing mice with fluorodeoxyuridine (FdUrd) to induce a thymidine synthesis block to enhance FLT tumor uptake through the salvage pathway. Methods FdUrd concentrations selected have been shown to efficiently induce the salvage pathway. In vitro studies were conducted on 1 human lymphoma and 2 human glioblastoma cell lines. Cells pretreated for 1h with 1µM FdUrd and control cells were incubated for 2h with FLT. Biodistributions were performed in SCID or nude mice bearing human lymphoma (Ramos) or glioblastoma (LN229) xenografts. 2.5 mg/kg FdUrd was injected iv 1h before FLT (1MBq/mouse). Animals were sacrificed 1 and 3h post FLT injection. Tissue uptake in mice was expressed in % of injected dose per gram (%ID/g). Results Pretreatment with FdUrd induced a 5.8fold increase of FLT uptake in the lymphoma xenografts at 1h (42.4±5.8 %ID/g in pretreated mice compared with 7.3±1.2 %ID/g in control mice). FLT uptake in FdUrd pretreated mice remained high at 3h with 41.3±5.8 %ID/g. Mice bearing glioblastoma xenografts showed a 2.6fold tumor uptake increase of FLT after FdUrd pretreatment. In vitro experiments demonstrated only weak cell uptake increase of FLT post FdUrd pretreatment (1.2 and 1.7fold). Conclusions In vivo results are promising for using FdUrd to enhance tumor uptake of FLT. Studies are ongoing to elucidate the difference in FLT tumor uptake response in vivo and in vitro.