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In Vivo Evaluation of 5-[¹⁸F]Fluoro-2'-deoxyuridine as Tracer for Positron Emission Tomography in a Murine Pancreatic Cancer Model

Departments of Nuclear Medicine [U. S., A. T. V., G. G., B. N., S. N. R.] and Internal Medicine I [M. W., F. R. G., R. M. S.], University of Ulm, 89081 Ulm, Germany

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[¹⁸F]-2'-deoxyuridine ([¹⁸F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor 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 [¹⁸F]FdUrd and 1 MBq of [¹⁸F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [¹⁸F]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 [¹⁸F]FdUrd as a tracer for the assessment of proliferation in vivo.

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