The investigational radioisotope, F-18 FLT (fluorothymidine), is showing promise in clinical trials in the ability to assess response to cancer treatment. Research into the clinical applications of the FLT radiotracer has been underway for over 10 years. After FDA approval for use in clinical trials, the molecular imaging community is holding much promise in the use of this tracer for assessment of cancer treatment.
While the most widely used PET tracer, F-18 FDG, exhibits glucose metabolism in cellular tissue, F-18 FLT is retained only in proliferating tissues. This difference in uptake can mean quite a lot when examining some applications of tumor assessment, such as brain imaging. Due to the high glucose metabolism in the brain, some lesions of the brain can be hard to assess using F-18 FDG imaging.
When using FLT imaging to assess chemotherapy response, serial imaging is indicated. Cell proliferation is expected to decrease after the first course of treatment. A baseline FLT study would be performed, and then a post-treatment study after the first course of treatment. The amount of uptake, and more importantly, the differences in the amount of uptake, will determine the effectiveness and response of the treatment.
Method of Uptake: How and why does F18 FLT incorporate itself into proliferating cells?
In order to understand the method of uptake of F-18 FLT, it is important to understand a few simple biochemical aspects:
1) Fluorothymidine is a thymidine (also called deoxythymidine) analogue
2) Thymidine is the nucleoside ‘T’ of DNA (composed of thymine and deoxyribose)
3) Every time a cell divides, it synthesizes its DNA to create a new cell: thymidine is used to create new DNA
4) This is why the thymidine analogue exhibits itself in proliferating cells and is retained: the radiolabeled thymidine analogue incorporates itself in the DNA of the newly created cells and remains there
In contrast to using F-18 FDG, where we see the metabolic state of the cells, we are able to use F-18 FLT to see if the cells are growing (or if growth is being inhibited due to therapy).