Accelerator mass spectrometry analysis of background (14)C-concentrations in human blood: aiming at reference data for further microdosing studies.
OBJECTIVE
Phase 0 clinical studies, which are known as microdose trials, are expected to promote drug development and reduce development costs. The accelerator mass spectrometry (AMS) system is expected to play an important role in the microdosing tests, as it is a highly sensitive measurement system that can be used to determine the drug concentrations in these tests. Using the AMS system, we measured the background (14)C-concentration in human blood and evaluated the data for use as a reference in microdose studies that administer (14)C-labeled compounds in humans.


METHODS
Blood samples of five healthy Japanese volunteers (three men, two women, median age 40.4 +/- 9.8 years) were collected around the same time and just prior to when the subjects ate a meal (between 12:00 noon and 2:00 pm). Centrifugal separations of blood that was allowed to clot and the plasma were performed at 503 g for 2 min at 4 degrees C. Background (14)C-concentration for each of the samples was measured using the AMS system. The Institute of Accelerator Analysis, which is the first contract research organization in Japan that is capable of providing AMS analysis services for carbon dating and bioanalysis work, performed the AMS analysis.


RESULTS
The mean (14)C-concentration in blood was 1.613 +/- 0.125 dpm/ml (men 1.668 +/- 0.114 dpm/ml, women 1.514 +/- 0.076 dpm/ml), in clots 2.373 +/- 0.087 dpm/ml (men 2.381 +/- 0.101 dpm/ml, women 2.357 +/- 0.060 dpm/ ml), and in plasma 0.648 +/- 0.049 dpm/ml (men 0.647 +/- 0.059 dpm/ml, women 0.649 +/- 0.032 dpm/ml). The coefficient variation (CV) for blood was 7.8% (men 6.9%, women 5.0%), for clots 3.7% (men 4.3%, women 2.5%), and for plasma 7.6% (men 9.1%, women 4.9%). The (14)C-concentrations of the clot and blood were higher than those of plasma. The (14)C-concentrations in the blood and plasma were slightly different between individuals when compared with the values for the clot, although the differences were quite small, with a CV value less than 7.8%.


CONCLUSIONS
Even though the (14)C-concentration differed only slightly between individuals, (14)C-concentrations of the clot and blood were higher than those of the plasma. Therefore, the variation and difference of the background data for blood and plasma might be of use as a reference for microdosing test evaluations.
Minamimoto
Ryogo
R
Department of Radiology, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. ryogom@yokohama-cu.ac.jp
Hamabe
Yoshimi
Y
Miyaoka
Teiji
T
Hara
Takamitsu
T
Yoshida
Keisuke
K
Oka
Takashi
T
Inoue
Tomio
T
D000328:Adult; D001417:Background Radiation; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards*; D002250:Carbon Radioisotopes / Q000097:blood*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards*; D008875:Middle Aged; D010315:Particle Accelerators; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002250:Carbon Radioisotopes