Abstract
BackgroundCimbi-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.ResultsThe 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.ConclusionThe 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.
Highlights
Cimbi-36 can be labeled with carbon-11 to form a positron emission tomography (PET) radioligand for imaging of serotonin 2A receptor (5-HT2AR) agonist binding in the human brain [1]. 5-HT2ARs are widely distributed in the cerebral cortex [2] and has been linked to neuropsychiatric disorders such as depression [3, 4]
We refrained from completing the last two planned 11C-Cimbi-36_5 scans, as the decision to use the 11C-Cimbi-36 labeling position for future 5HT2AR imaging studies was made before the completion of this study [15], regardless of the dosimetry outcome
The Serotonin 2A receptor (5-HT2A) receptor agonist PET radioligand 11CCimbi-36 has a favorable radiation dosimetry profile with an effective dose of 5.5 μSv/MBq, which allows for injection of 1.8 GBq per study in healthy volunteers, making 11C-Cimbi-36 eligible for studies involving a series of PET scans in a single subject
Summary
Cimbi-36 can be labeled with carbon-11 to form a positron emission tomography (PET) radioligand for imaging of serotonin 2A receptor (5-HT2AR) agonist binding in the human brain [1]. 5-HT2ARs are widely distributed in the cerebral cortex [2] and has been linked to neuropsychiatric disorders such as depression [3, 4]. Cimbi-36 can be labeled with carbon-11 to form a positron emission tomography (PET) radioligand for imaging of serotonin 2A receptor (5-HT2AR) agonist binding in the human brain [1]. The Cimbi-36 molecule (N-(2-methoxybenzyl)-2,5-dimethoxy-4-bromophenethylamine) itself acts as an agonist on the 5-HT2AR and is used in pharmacological doses as a recreational drug, known as 25B-NBOMe, belonging to the class of new psychoactive substances [7]. 11C-labeled Cimbi-36 is presently the only agonist radioligand available for imaging the 5-HT2AR [8], and it is known that agonists and antagonists interact in different modes with the receptor [9]. 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. We investigated human biodistribution and radiation dosimetry of the radioligand with two different radiolabeling positions. 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
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