Kinetic analysis of the cannabinoid-1 receptor PET tracer [(18)F]MK-9470 in human brain.
OBJECTIVE
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 [(18)F]MK-9470 in human brain.


METHODS
[(18)F]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.


CONCLUSIONS
[(18)F]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 [(18)F]MK-9470 plasma kinetics can be assessed using a few venous samples.
Sanabria-Bohórquez
Sandra Marina
SM
Imaging, Merck Research Laboratories, Sumneytown Pike WP44D-2, West Point, PA 19486, USA. sandra_sanabria@merck.com
Hamill
Terence G
TG
Goffin
Karolien
K
De Lepeleire
Inge
I
Bormans
Guy
G
Burns
H Donald
HD
Van Laere
Koen
K
D000328:Adult; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D055815:Young Adult
C528731:MK-9470; D011725:Pyridines; D011849:Radioactive Tracers; D043884:Receptor, Cannabinoid, CB1