Synthesis and evaluation of radiolabeled antagonists for imaging of beta-adrenoceptors in the brain with PET.
Five potent, lipophilic beta-adrenoceptor antagonists (carvedilol, pindolol, toliprolol and fluorinated analogs of bupranolol and penbutolol) were labeled with either carbon-11 or fluorine-18 and evaluated for cerebral beta-adrenoceptor imaging in experimental animals. The standard radioligand for autoradiography of beta-adrenoceptors, [125I]-iodocyanopindolol, was also included in this survey. All compounds showed either very low uptake in rat brain or a regional distribution that was not related to beta-adrenoceptors, whereas some ligands did display specific binding in heart and lungs. Apparently, the criteria of a high affinity and a moderately high lipophilicity were insufficient to predict the suitability of beta-adrenergic antagonists for visualization of beta-adrenoceptors in the central nervous system.
Doze
Petra
P
PET-Center, Groningen University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Elsinga
P H
PH
Maas
B
B
Van Waarde
A
A
Wegman
T
T
Vaalburg
W
W
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002046:Bupranolol / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002227:Carbazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D000077261:Carvedilol; D005462:Fluorine Radioisotopes; D008297:Male; D023421:Models, Animal; D009928:Organ Specificity; D010869:Pindolol / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011412:Propanolamines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011433:Propranolol / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; D002046:Bupranolol; D011433:Propranolol; D010869:Pindolol; C073327:toliprolol