Correlation analysis of measurement result between accelerator mass spectrometry and gamma counter.

The guidelines for microdosing in clinical trials were published in Japan in 2008 following the guidelines of the European Medicines Agency and the Food and Drug Administration. They recommend utilizing accelerator mass spectrometry (AMS) and positron emission tomography as candidates for monitoring drug metabolites in preclinical studies. We correlate the two methods by measuring appropriately labeled tissue samples from various mouse organs using both AMS and gamma counter. First, we measured the ¹⁴C background levels in mouse organs using the AMS system. We then clarified the relationship between AMS and gamma counter by simultaneously administering ¹⁴C-2-fluoro-2-deoxyglucose (¹⁴C-FDG) and ¹⁸F-2-fluoro-2-deoxyglucose (¹⁸F-FDG). Tissue distribution was examined after 30 min, 1 h, 2 h and 4 h using the AMS system for ¹⁴C-FDG and gamma counter for ¹⁸F-FDG. Background ¹⁴C levels were subtracted from the data obtained with radiotracer administration. The background ¹⁴C concentration differed with tissue type measured. Background ¹⁴C concentration in mouse liver was higher than in other organs, and was approximately 1.5-fold that in blood. The correlation coefficient ( r) of the measurements between AMS (¹⁴C-FDG) and gamma counter (¹⁸F-FDG) was high in both normal (0.99 in blood, 0.91 in brain, 0.61 in liver and 0.78 in kidney) and tumor-bearing mice (0.95 in blood and 0.99 in tumor). The clearance profile of ¹⁸F-FDG was nearly identical to that of ¹⁴C-FDG measured with AMS. Accelerator mass spectrometry analysis has an excellent correlation with biodistribution measurements using gamma counter. Our results suggest that the combination of AMS and PET can act as a complementary approach to accelerate drug development. [ABSTRACT FROM AUTHOR]