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Minamimoto R.,Yokohama City University | Hamabe Y.,Institute of Accelerator Analysis IAA Ltd. | Cheng C.,Yokohama City University | Shimoda M.,Institute of Accelerator Analysis IAA Ltd. | And 2 more authors.
Annals of Nuclear Medicine | Year: 2010

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. © 2009 The Japanese Society of Nuclear Medicine.


Minamimoto R.,Yokohama City University | Hamabe Y.,Institute of Accelerator Analysis IAA Ltd. | Miyaoka T.,Institute of Accelerator Analysis IAA Ltd. | Theeraladanon C.,Yokohama City University | And 3 more authors.
Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms | Year: 2010

The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground 14C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient (r) of the measurements using PET ( 18F-FDG) and AMS ( 14C-FDG) were quite high at 0.97 (Y = 7.54E - 05X + 0.02, p < 0.001). The blood clearance profile of 18F-FDG was nearly identical with that of 14C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method. © 2009 Elsevier B.V. All rights reserved.

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