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 - 2014/7
Y1 - 2014/7
N2 - [ 11 C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A) 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 [ 11 C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT 2A receptors with [ 11 C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [ 11 C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [ 11 C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT 2A receptor antagonist ketanserin before a second PET scan significantly decreased [ 11 C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [ 11 C]Cimbi-36 binding is selective for 5-HT 2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT 2A receptors in the human brain. Thus, we here describe [ 11 C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT 2A receptors in the human brain.
AB - [ 11 C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A) 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 [ 11 C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT 2A receptors with [ 11 C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [ 11 C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [ 11 C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT 2A receptor antagonist ketanserin before a second PET scan significantly decreased [ 11 C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [ 11 C]Cimbi-36 binding is selective for 5-HT 2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT 2A receptors in the human brain. Thus, we here describe [ 11 C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT 2A receptors in the human brain.
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
SN - 0271-678X
VL - 34
SP - 1188
EP - 1196
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
ER -
