Ohya_2012_Nucl.Med.Commun_33_1019

OBJECTIVE: The aim of this study was to develop a method to predict a tracer's alpha-value in the human brain on the basis of animal data. The alpha-value is the ratio of the conversion rate and the back-diffusion rate (k3/k2) and is one of the critical kinetic features of the detection sensitivity of target molecule activity, such as enzyme activity, in the measurement of PET and single-photon emission computed tomography using an irreversible-type radiotracer. METHOD: The alpha-value in the rat brain was estimated by a simultaneous assay of the tracer uptake and the target biochemical activity using N-[C]-methylpiperidin-4-yl acetate ([C]MP4A) and N-[C]-methylpiperidin-4-yl propionate ([C]MP4P) as test tracers, both of which are metabolic trapping tracers for measurement of brain acetylcholinesterase. The alpha-value in humans was then extrapolated from the alpha-value in rats by considering the differences between the species. The predicted human alpha-values were compared with those obtained from the kinetic analyses of human PET studies using [C]MP4A and [C]MP4P. RESULT: The alpha-values in the human brain cortex were predicted to be 0.51+/-0.1 for MP4A and 0.25+/-0.05 for MP4P. These results were close to values reported in other PET studies: 0.48+/-0.1 to 0.73+/-0.2 for MP4A and 0.15+/-0.04 to 0.18+/-0.04 for MP4P. CONCLUSION: The alpha-value predicted by this method would be used for practical selection or development of irreversible-type radiotracers for human use.