Detection of muscarinic receptors in the human lung using PET.
The characterization of pulmonary muscarinic receptors with PET is still in its infancy. Because approximately 70% of the lungs consists of air and pulmonary muscarinic receptor densities are low, ligands with high receptor affinity are required to obtain reasonable signal-to-noise ratios on PET images. Therefore, the potent 11C-labeled muscarinic antagonist N-methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide ([R]-VC-002) was developed. We administered this radioligand to four healthy human volunteers to examine its suitability for studying pulmonary muscarinic receptors in vivo.


METHODS
[11C]VC-002 (185 MBq, specific activity > 7.4 TBq/mmol) was intravenously injected on 2 separate days, with an interval of at least 1 wk. On the first day the volunteers were not pretreated, but on the second day they received the anticholinergic glycopyrronium bromide (Robinul; 2 x 0.1 mg intravenous) 25 and 30 min before the injection of the radiopharmaceutical. C[15O]O scans (approximately 740 MBq [20 mCi] by inhalation) were acquired before the receptor scan to calculate pulmonary blood volume.


RESULTS
On PET images of the thorax, the lungs were clearly visible. After the volunteer was pretreated with glycopyrronium bromide, pulmonary uptake of the radioligand was reduced to 32%+/-12% of the control value at 60 min postinjection and the lungs could no longer be seen. (R)-[11C]-VC-002 was rapidly cleared from plasma and was slowly metabolized during the time course (60 min) of the PET scan. The fraction of radioligand representing parent compound decreased from 99.9% at the time of injection to 82% at 40-60 min postinjection, both in the presence and absence of Robinul. Pulmonary tissue-to-plasma ratios, calculated on a count-per-minute-per-gram basis, reached a plateau value of 17.8+/-1.2 at 40-50 min postinjection.


CONCLUSIONS
[11C]VC-002 appears to be suitable for in vivo studies of pulmonary cholinoceptors.
Visser
T J
TJ
PET Center, Department of Pulmonary Diseases, Groningen University Hospital, The Netherlands.
van Waarde
A
A
van der Mark
T W
TW
Kraan
J
J
Ensing
K
K
Willemsen
A T
AT
Elsinga
P H
PH
Vaalburg
W
W
D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D008657:Metabolic Clearance Rate; D018727:Muscarinic Antagonists; D010648:Phenylacetates / Q000493:pharmacokinetics; D010880:Piperidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D008024:Ligands; D018727:Muscarinic Antagonists; D010648:Phenylacetates; D010880:Piperidines; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic; C120923:VC 002