First-in-human imaging using [¹¹C]MDTC: a radiotracer targeting the cannabinoid receptor type 2.

Area of Science:

• Neuroscience
• Radiochemistry
• Pharmacology

Background:

• Cannabinoid receptor type 2 (CB2R) is implicated in neuroinflammation.
• Developing specific PET radiotracers for CB2R is crucial for studying neurological conditions.

Purpose of the Study:

• To evaluate the safety, tolerability, and pharmacokinetic properties of [11C]MDTC, a novel PET radiotracer for CB2R, in healthy human subjects.
• To assess the test-retest reproducibility of [11C]MDTC binding in the brain.
• To determine the radiation dosimetry of [11C]MDTC.

Main Methods:

• First-in-human, dynamic 90-min PET scans with intravenous [11C]MDTC in 10 healthy adults.
• Test-retest reproducibility assessed in 5 participants.
• Kinetic analysis using a three-tissue compartment model.
• Whole-body PET/CT scans in 4 additional adults for dosimetry.

Main Results:

• [11C]MDTC was well-tolerated in all participants.
• A three-tissue compartment model best described brain kinetics, accounting for brain-penetrant radiometabolites.
• Low regional distribution volume (V_T) values indicated minimal CB2R expression in the healthy brain.
• Test-retest variability for V_T was 9.91%.
• The effective dose was calculated to be 5.29 μSv/MBq.

Conclusions:

• [11C]MDTC demonstrates favorable safety and pharmacokinetic profiles for PET imaging in the human brain.
• Low V_T values suggest limited utility for imaging low-density CB2R in healthy subjects.
• Further studies are recommended to characterize [11C]MDTC radiometabolites before its application in conditions with high CB2R expression, such as neuroinflammation.