Tj. Visser et al., Synthesis and biodistribution of [C-11]procaterol, a beta(2)-adrenoceptor agonist for positron emission tomography, APPL RAD IS, 52(4), 2000, pp. 857-863
The potent, subtype-selective radioligand (+/-)-erythro-5-(1-hydroxy-2-[C-1
1]isopropyl-aminobutyl)-8-hydroxy-carbostyril ([C-11]procaterol) was synthe
sized and evaluated for visualization of pulmonary beta(2)-adrenoceptors wi
th positron emission tomography (PET). Procaterol was labelled by reductive
alkylation of the desisopropyl precursor with [C-11]acetone under the infl
uence of NaCNBH3 and acetic acid. Synthesis and HPLC purification were perf
ormed in 34 min. Specific activities ranged from 26.5-39.3 TBq (about 700-1
000 Ci)/mmol and the radiochemical yield was 2.4-8.6% (corrected for decay)
.
Biodistribution studies were performed in male Wistar rats which were eithe
r untreated or predosed with (D,L)-propranolol hydrochloride (beta-adrenoce
ptor 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 i
soprenaline (B-adrenoceptor agonist, 15 mg/kg). Specific binding was observ
ed in lungs, spleen and red blood cells, tissues known to contain beta(2)-a
drenoceptors. Pulmonary binding was blocked by propranolol, ICI 118551 and
isoprenaline, but not by CGP 20712A. This binding pattern is consistent wit
h the beta(2) selectivity of the adioligand.
The clearance of [C-11]procaterol was biphasic, with a rapid distribution p
hase (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-procate
rol the most active of 4 stereoisomers, may produce better results, [C-11]p
rocaterol seems unsuitable for beta-adrenoceptor imaging. (C) 2000 Elsevier
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