TY - JOUR

T1 - Serotonin 2A receptor agonist binding in the human brain with [C]Cimbi-36

AU - Ettrup, A.

AU - da Cunha-Bang, S.

AU - McMahon, Barry P.

AU - Lehel, S.

AU - Dyssegaard, A.

AU - Skibsted, A.W.

AU - Jørgensen, Louise Møller

AU - Hansen, M.

AU - Baandrup, A.O.

AU - Bache, S.

AU - Svarer, C.

AU - Kristensen, Jesper Langgaard

AU - Gillings, N.

AU - Madsen, Jacob

AU - Knudsen, G.M.

PY - 2014/4/30

Y1 - 2014/4/30

N2 - [C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT receptor antagonist ketanserin before a second PET scan significantly decreased [C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [C]Cimbi-36 binding is selective for 5-HT receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT receptors in the human brain. Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68.

AB - [C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT receptor antagonist ketanserin before a second PET scan significantly decreased [C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [C]Cimbi-36 binding is selective for 5-HT receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT receptors in the human brain. Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68.

UR - http://www.scopus.com/inward/record.url?scp=84898731075&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2014.68

DO - 10.1038/jcbfm.2014.68

M3 - Journal article

C2 - 24780897

AN - SCOPUS:84903768966

VL - 34

SP - 1188

EP - 1196

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

ER -