Evaluation of the kappa-opioid receptor-selective tracer [(11)C]GR103545 in awake rhesus macaques.
OBJECTIVE
The recent development in radiosynthesis of the (11)C-carbamate function increases the potential of [(11)C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET. In the present study, [(11)C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound.


METHODS
Regional brain uptake kinetics of [(11)C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [(11)C]GR103545 was determined in cells transfected with cloned human opioid receptors.


RESULTS
In vitro binding assays demonstrated a high affinity of GR103545 for kappa-OR (K(i) = 0.02 +/- 0.01 nM) with excellent selectivity over mu-OR (6 x 10(2)-fold) and) delta-OR (2 x 10(4)-fold). PET imaging revealed a volume of distribution (V(T)) pattern consistent with the known distribution of kappa-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum.


CONCLUSIONS
[(11)C]GR103545 is selective for kappa-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET.
Schoultz
Bent W
BW
Department of Chemistry, University of Oslo, Oslo, Norway.
Hjornevik
Trine
T
Willoch
Frode
F
Marton
János
J
Noda
Akihiro
A
Murakami
Yoshihiro
Y
Miyoshi
Sosuke
S
Nishimura
Shintaro
S
Arstad
Erik
E
Drzezga
Alexander
A
Matsunari
Ichiro
I
Henriksen
Gjermund
G
D000818:Animals; D002250:Carbon Radioisotopes; D008253:Macaca mulatta; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism*; D011849:Radioactive Tracers; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013379:Substrate Specificity; D014851:Wakefulness
D002250:Carbon Radioisotopes; D010879:Piperazines; D011759:Pyrrolidines; D011849:Radioactive Tracers; D017473:Receptors, Opioid, kappa; C071609:GR 89696