Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions

Abstract Background Cimbi-36 can be 11C-labeled to form an agonist radioligand used for positron emission tomography (PET) imaging of the 5-HT2A receptor in the brain. In its non-labeled form (25B-NBOMe), it is used as a recreational drug that can lead to severe adverse effects, in some cases, with fatal outcome. We investigated human biodistribution and radiation dosimetry of the radioligand with two different radiolabeling positions. Seven healthy volunteers underwent dynamic 120-min whole-body PET scans (injection of 581 ± 16 MBq, n = 5 for 11C-Cimbi-36; 593 ± 14 MBq, n = 2 for 11C-Cimbi-36_5). Time-integrated activity coefficients (TIACs) from time-activity curves (TACs) of selected organs were used as input into the OLINDA/EXM software to obtain dosimetry information for both 11C-labeling positions of Cimbi-36. Results The effective dose was only slightly higher for 11C-Cimbi-36 (5.5 μSv/MBq) than for 11C-Cimbi-36_5 (5.3 μSv/MBq). Standard uptake value (SUV) curves showed higher uptake of 11C-Cimbi-36 in the pancreas, small intestines, liver, kidney, gallbladder, and urinary bladder compared with 11C-Cimbi-36_5, reflecting differences in radiometabolism for the two radioligands. Variability in uptake in excretory organs for 11C-Cimbi-36 points to inter-individual differences with regard to metabolic rate and route. Surprisingly, moderate uptake was found in brown adipose tissue (BAT) in four subjects, possibly representing specific 5-HT2A/2C receptor binding. Conclusion The low effective dose of 5.5 μSv/MBq allows for the injection of up to 1.8 GBq for healthy volunteers per study (equivalent to 3 scans if injecting 600 MBq) and still stay below the international guidelines of 10 mSv, making 11C-Cimbi-36 eligible for studies involving a series of PET scans in a single subject. The biodistribution of Cimbi-36 (and its metabolites) may also help to shed light on the toxic effects of 25B-NBOMe when used in pharmacological doses in recreational settings.