Synthesis and biodistribution of [11C]procaterol, a β2-adrenoceptor agonist for positron emission tomography
| Autor: | Philippus Elsinga, Ton J. Visser, P Doze, EA van der Wouden, W Vaalburg, van Aren Waarde |
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| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2000 |
| Předmět: |
Male
Agonist Biodistribution medicine.medical_specialty positron emission tomography ADRENERGIC-RECEPTOR Metabolic Clearance Rate Hydrochloride Procaterol medicine.drug_class Adrenergic beta-Antagonists Propranolol lung Radioligand Assay chemistry.chemical_compound beta(2)-adrenoceptor Isoprenaline Internal medicine medicine Radioligand Animals PROCATEROL Tissue Distribution Carbon Radioisotopes Rats Wistar DEPOSITION agonist SOLEUS MUSCLE FORMOTEROL Radiation Antagonist BETA-ADRENOCEPTOR STIMULANT Adrenergic beta-Agonists CARDIOVASCULAR-SYSTEM Rats Endocrinology chemistry [C-11]procaterol VISUALIZATION Receptors Adrenergic beta-2 RADIOTRACER OPC-2009 Tomography Emission-Computed medicine.drug |
| Zdroj: | Applied Radiation and Isotopes, 52(4), 857-863. PERGAMON-ELSEVIER SCIENCE LTD |
| ISSN: | 0969-8043 |
| DOI: | 10.1016/s0969-8043(99)00267-5 |
| Popis: | The potent, subtype-selective radioligand (+/-)-erythro-5-(1-hydroxy-2-[C-11]isopropyl-aminobutyl)-8-hydroxy-carbostyril ([C-11]procaterol) was synthesized and evaluated for visualization of pulmonary beta(2)-adrenoceptors with positron emission tomography (PET). Procaterol was labelled by reductive alkylation of the desisopropyl precursor with [C-11]acetone under the influence of NaCNBH3 and acetic acid. Synthesis and HPLC purification were performed in 34 min. Specific activities ranged from 26.5-39.3 TBq (about 700-1000 Ci)/mmol and the radiochemical yield was 2.4-8.6% (corrected for decay).Biodistribution studies were performed in male Wistar rats which were either untreated or predosed with (D,L)-propranolol hydrochloride (beta-adrenoceptor antagonist, 2.5 mg/kg), ICI 118551 (beta(2)-adrenoceptor antagonist, 0.15 mg/ kg), CGP 20712A (beta(1)-adrenoceptor antagonist, 0.15; mg/kg) or isoprenaline (B-adrenoceptor agonist, 15 mg/kg). Specific binding was observed in lungs, spleen and red blood cells, tissues known to contain beta(2)-adrenoceptors. Pulmonary binding was blocked by propranolol, ICI 118551 and isoprenaline, but not by CGP 20712A. This binding pattern is consistent with the beta(2) selectivity of the adioligand.The clearance of [C-11]procaterol was biphasic, with a rapid distribution phase (t(1/2) 0.17 min) representing 90% of the injected dose followed by an elimination phase (t(1/2) 18.1 min). About 45% of the plasma radioactivity was unmetabolized procaterol at 15 min postinjection.In a dynamic PET-study, the lungs of untreated control rats could barely be detected and total/non-specific binding ratios rose to only 1.2 at 20 min postinjection. Although labelling and administration of (-) erythro-procaterol the most active of 4 stereoisomers, may produce better results, [C-11]procaterol seems unsuitable for beta-adrenoceptor imaging. (C) 2000 Elsevier Science Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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