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 (14)C background levels in mouse organs using the AMS system. We then clarified the relationship between AMS and gamma counter by simultaneously administering (14)C-2-fluoro-2-deoxyglucose ((14)C-FDG) and (18)F-2-fluoro-2-deoxyglucose ((18)F-FDG). Tissue distribution was examined after 30 min, 1 h, 2 h and 4 h using the AMS system for (14)C-FDG and gamma counter for (18)F-FDG. Background (14)C levels were subtracted from the data obtained with radiotracer administration.

The background (14)C concentration differed with tissue type measured. Background (14)C 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 ((14)C-FDG) and gamma counter ((18)F-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 (18)F-FDG was nearly identical to that of (14)C-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.