Abstract
Purpose
Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [18F]MK-9470 in human brain.
Methods
[18F]MK-9470 data were analysed using reversible models and the distribution volume V T and V ND k 3 (V ND k 3 = K 1 k 2) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K i and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined.
Results
A reversible two-tissue compartment model using a global k 4 value was necessary to describe brain kinetics. Both V T and V ND k 3 were estimated satisfactorily and their test–retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K i. The linear relationship between K i and V ND k 3 demonstrated that K i or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test–retest variability of K i and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics.
Conclusion
[18F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [18F]MK-9470 plasma kinetics can be assessed using a few venous samples.
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Acknowledgments
The authors would like to thank Tom Muylle and Dr. Patrick Dupont for their helpful suggestions.
Conflicts of interest
S.M.S.B., T.G.H. and I.D.L. are employees of Merck Inc., Co.
H.D.B. is a consultant to Merck Inc., Co.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00259-010-1395-3
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Sanabria-Bohórquez, S.M., Hamill, T.G., Goffin, K. et al. Kinetic analysis of the cannabinoid-1 receptor PET tracer [18F]MK-9470 in human brain. Eur J Nucl Med Mol Imaging 37, 920–933 (2010). https://doi.org/10.1007/s00259-009-1340-5
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DOI: https://doi.org/10.1007/s00259-009-1340-5