title: A method to predict the ratio of the tracer conversion rate to the tracer back-diffusion rate of an irreversible-type radiotracer in humans by preclinical evaluations.
abstract: OBJECTIVE
  The aim of this study was to develop a method to predict a tracer's α-value in the human brain on the basis of animal data. The α-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.
  
  
  METHODS
  The α-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 α-value in humans was then extrapolated from the α-value in rats by considering the differences between the species. The predicted human α-values were compared with those obtained from the kinetic analyses of human PET studies using [C]MP4A and [C]MP4P.
  
  
  RESULTS
  The α-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.
  
  
  CONCLUSIONS
  The α-value predicted by this method would be used for practical selection or development of irreversible-type radiotracers for human use.
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. ohya@nirs.go.jp
authors: Tomoyuki
authors: T
authors: Ohya
authors: Ming-Rong
authors: MR
authors: Zhang
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Kiyoshi
authors: K
authors: Fukushi
authors: Tatsuya
authors: T
authors: Kikuchi
authors: Toshiaki
authors: T
authors: Irie
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010880:Piperidines / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011422:Propionates / Q000378:metabolism*; D011849:Radioactive Tracers; D051381:Rats; D015203:Reproducibility of Results; D013045:Species Specificity
chemical_list: D000085:Acetates; C100518:N-methyl-4-piperidyl acetate; C100519:N-methyl-4-piperidyl propionate; D010880:Piperidines; D011422:Propionates; D011849:Radioactive Tracers; D000110:Acetylcholinesterase