In vivo evaluation of 5-[18F]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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-05, Vol.61 (10), p.3853-3857
Main Authors: SEITZ, Ulrike, WAGNER, Martin, VOGG, Andreas T, GLATTING, Gerhard, NEUMAIER, Bernd, GRETEN, Florian R, SCHMID, Roland M, RESKE, Sven N
Format: Article
Language:English
Subjects:
Animal tumors. Experimental tumors
Animals
Biological and medical sciences
Cell Division - physiology
Disease Models, Animal
Disease Progression
Experimental digestive system and abdominal tumors
Floxuridine - chemical synthesis
Floxuridine - pharmacokinetics
Fluorodeoxyglucose F18
Genes, p53 - genetics
Medical sciences
Mice
Mice, Transgenic
Pancreatic Neoplasms - diagnostic imaging
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Radionuclide Imaging
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - pharmacokinetics
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Thymidine Kinase - biosynthesis
Thymidine Kinase - genetics
Thymidylate Synthase - biosynthesis
Thymidylate Synthase - genetics
Transforming Growth Factor alpha - genetics
Tumors
Up-Regulation
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Summary: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.
ISSN:0008-5472
1538-7445