In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model.
We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.
Seitz
U
U
Department of Nuclear Medicine, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.ulrike.seitz@medizin.uni-ulm.de
Wagner
M
M
Vogg
A T
AT
Glatting
G
G
Neumaier
B
B
Greten
F R
FR
Schmid
R M
RM
Reske
S N
SN
D000818:Animals; D002455:Cell Division / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005467:Floxuridine / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18; D016158:Genes, p53 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics; D015854:Up-Regulation
D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D016211:Transforming Growth Factor alpha; D005467:Floxuridine; D019788:Fluorodeoxyglucose F18; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; C092717:thymidine kinase 1