General Tracer Class: Investigational Diagnostic PET Radiopharmaceutical.
Target: Proliferating tissue, primarily cancers.
Mechanism for in vivo retention: Fluorothymidine is an analog of the nucleoside thymidine (deoxythymidine) but the 3’-F atom prevents FLT from following the full biochemical pathway of thymidine. FLT is transported from the blood into cells by active transport, it does not freely diffuse across the cell membrane. Once in the cell, FLT is a substrate for thymidine kinase I (TK1) and is phosphorylated but is not incorporated into DNA. The assumption is that the concentration of FLT nucleotides in cells is proportional to TK1 activity and therefore to cellular proliferation. Phosphorylated FLT cannot exit the cell. FLT is not a substrate for thymidine phosphorylase and so is not significantly degraded in vivo and is retained in the cells. One advantage of FLT is that it is only a substrate for TK1 and not for mitochondrial TK2 and so it is a more specific tracer compared with other fluorinated tracers for cellular proliferation.
Metabolism: FLT is not dephosphorylated in vivo but conjugated FLT is cleared via the kidneys and excretion in the urine.
Recommended Activity and / Allowable mass: As FLT is investigational, there is no current set standard for the amount of radiation to be administered or the maximum nonradioactive FLT that may be administered. Typical activities are 185 to 370 MBq (5 to 10mCi) maximum injected dose. The IND held by NIH requires a radiochemical purity of no less than 95% and no more than 5 mcg of nonradioactive FLT and no more than 5 mcg of other UV-absorbing impurities.
Dosimetry: The effective dose equivalent is reported to be 0.028 ± 0.012 mSv/MBq for the standard adult male and 0.033 ± 0.012 mSv/MBq for the standard adult female. The critical organ is the urinary bladder wall and the dose depends on the voiding. schedule: 0.18 mGy/MBq in males with voiding at 6 hrs and 0.08 mGy/MBq with voiding at 2 and 6 hrs post injection. (J NuclMed 44:1482,2003).