Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

Background: 18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Methods: Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). Results: No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 � 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. Conclusion: This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.This study was supported by NIH grant R01 CA115559, 1R01 CA107264, and 1R01 CA80907