Human biodistribution and radiation dosimetry of the 5-HT(2A) receptor agonist Cimbi-36 labeled with carbon-11 in two positions

BACKGROUND: Cimbi-36 can be (11)C-labeled to form an agonist radioligand used for positron emission tomography (PET) imaging of the 5-HT(2A) 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 (11)C-Cimbi-36; 593 ± 14 MBq, n = 2 for (11)C-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 (11)C-labeling positions of Cimbi-36. RESULTS: The effective dose was only slightly higher for (11)C-Cimbi-36 (5.5 μSv/MBq) than for (11)C-Cimbi-36_5 (5.3 μSv/MBq). Standard uptake value (SUV) curves showed higher uptake of (11)C-Cimbi-36 in the pancreas, small intestines, liver, kidney, gallbladder, and urinary bladder compared with (11)C-Cimbi-36_5, reflecting differences in radiometabolism for the two radioligands. Variability in uptake in excretory organs for (11)C-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-HT(2A/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 (11)C-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-019-0527-4) contains supplementary material, which is available to authorized users.