Investigation of [fluorine-18]fluoro-L-thymidine with positron emission tomography to assess radiotherapy response.

摘要

With the rapid growth of positron emission tomography (PET) in the field of oncology, there is a great need for cancer-specific radiopharmaceuticals. The standard oncology radiopharmaceutical, 18F-fluorodeoxyglucose (18F-FDG), is based glucose metabolism and used for the detection and staging of many types of cancer. However, 18F-FDG is far from specific to tumor sites and its uptake in macrophages as well as in granulation and inflamed tissues hinder effective assessment of radiotherapy response. 11C-thymidine has been used to image cellular proliferation in vivo for twenty years, but degradation of the tracer in the body means that arterial blood sampling is needed to do metabolite analysis for image correction. Also, the short half-life (t1/2 = 20 minutes) of carbon-11 limits 11C-thymidine scanning to sites that have a cyclotron and radiochemistry lab nearby. A thymidine analog labeled with fluorine-18 would resolve the problems associated with 11C-thymidine PET. To that end, 18F-fluoro-L-thymidine ( 18F-FLT) has been developed to provide a measure of cellular proliferation in vivo using PET.; Existing synthetic methods of 18F-FLT production were implemented using three different precursors: 2,3'-anhydrothymidine, 5'-O-(4,4'-dimethoxytrityl)-2,3 '-anhydrothymidine and 3-N-t-butoxycarbonyl-[5 '-O-(4,4'-dimethoxytrityl)-2' -deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta- D-threopentofuranosyl]thymine. Once implemented, various parameters were adjusted in an attempt to increase the radiochemical yield. A microwave "steeplechase" was performed in order to test the abilities of three different single mode microwave cavities. The winning microwave cavity was then used in 18F-FLT syntheses to increase the decay-corrected radiochemical yield in comparison to conventional heating. Once the chemistry was reliable enough to provide single study quantities of 18F-FLT, the ability to assess radiotherapy response using 18F-FLT was explored in a canine model. The animals were imaged before and during radiotherapy treatment to see if 18F-FLT could measure early response to the anti-cancer treatment using SUV and Patlak analysis techniques.