Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography

PurposeCannabinoid subtype 1 (CB1) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB1 receptors with two PET radioligands: 11C-MePPEP and 18F-FMPEP-d2. Here we describe the biodistribution and dosimetry estimates for these two radioligands.MethodsSeven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with 11C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with 18F-FMPEP-d2. Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for 18F-FMPEP-d2.ResultsThe effective doses of 11C-MePPEP and 18F-FMPEP-d2 are 4.6 and 19.7 μSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of 11C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from 18F-FMPEP-d2 showed both hepatobiliary and urinary excretion.Conclusion11C-MePPEP and 18F-FMPEP-d2 yield an effective dose similar to other PET radioligands labeled with either 11C or 18F. The high uptake in brain confirms the utility of these two radioligands to image CB1 receptors in brain, and both may also be useful to image CB1 receptors in the periphery.