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Cited by 10Radiopharmaceutical Chemistry and ApplicationsMedical Imaging Techniques and ApplicationsRadiation Dose and Imaging

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

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Johansen, Annette, Holm, Søren, Dall, Bente, Keller, Sune, Kristensen, Jesper L., Knudsen, Gitte M., Hansen, Hanne D.·2019·EJNMMI Research
DOI 10.1186/s13550-019-0527-4PMC PMC6669221
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Abstract

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. 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. 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.

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  • Metabolism of [11C]-Cimbi-36 in humans is characterized by loss of the [11C]-methoxy label or demethylation of the other methoxygroup, yielding a relatively hydrophobic radiometabolite.

    “The metabolism of [11C]-Cimbi-36 (38) in humans is characterized by loss of the [11C]-methoxy label (generating [11C]-formaldehyde) or demethylation of the other methoxygroup, yielding a relatively hydrophobic radiometabolite [93].”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [93]

    The Discussion’s “Biodistribution, pharmacology, and metabolism” section describes O-demethylation in humans and identifies a radiometabolite fraction likely containing [11C]-formaldehyde. It also identifies a second fraction as a [11C]-glucuronide conjugate, but does not describe the resulting radiometabolite as relatively hydrophobic; it calls the first fraction small and polar. No page number is available in our copy. (LLM, conf=0.87)

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Metadata

Authors
Johansen, A., Holm, S., Dall, B., Keller, S., Kristensen, J. L., Knudsen, G. M., & Hansen, H. D.
Affiliations
  • University of Copenhagen (DK)
  • Rigshospitalet (DK)
Corresponding author
Knudsen, Gitte M.
ORCID
Venue
EJNMMI Research
Publisher
Springer Science and Business Media LLC
Published
2019-07-31
Volume
9
Issue
1
Pages
71-71
ISSN
2191-219X (ISSN-L)
DOI
10.1186/s13550-019-0527-4
PMC
PMC6669221
OpenAlex
W2965802642
Cited by
10
References
5
Citations by year
2026: 1 · 2023: 3 · 2022: 4 · 2021: 2
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
Locations
  • EJNMMI Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Lundbeckfonden
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiation Dose and Imaging
Keywords
5-HT2A receptor, carbon-11 radiolabeling, radioligand biodistribution, radiation dosimetry, effective dose, radiometabolism, NBOMe, brown adipose tissue, 5-HT2C receptor, positron emission tomography, time-integrated activity coefficients, OLINDA/EXM, interindividual variability

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