Preliminary evaluation of 2-[4-[3-tert-butylamino)-2-hydroxypropoxy]phenyl]-3-methyl-6-me thoxy-4(3H)-quinazolinone ([+/-]HX-CH 44) as a selective beta1-adrenoceptor ligand for PET.
(+/-)-3-[11C]Methyl-2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6 -methoxy-4(3H) quinazolinone ([+/-]-[11C]HX-CH 44) was labeled with carbon-11 using [11C]iodomethane with the corresponding N-demethylated precursor. Then, 30-90 mCi (1.10-3.33 GBq) of pure [11C]HX-CH 44 were obtained 30 min after end of bombardment with specific radioactivities of 500-1,400 mCi/micromol (18.5-51.8 GBq/micromol). Myocardial uptake in dogs was 0.340+/-0.043 pmol/mL tissue per nanomole injected, 10-15 min postinjection. Heart-to-lung ratio was 3 from the 5th to the 30th minute. Only 35% of the myocardial radioactivity could be displaced. Tissue uptake could not be blocked with appropriate compounds. Therefore, (+/-)-[11C]HX-CH 44 does not appear to be a suitable ligand for the study of myocardial beta1-adrenoceptors in positron emission tomography.
Valette
H
H
Department de Recherche Medicale, Service Hospitalier Frederic Joliot, Orsay, France.
Dollé
F
F
Guenther
I
I
Demphel
S
S
Rasetti
C
C
Hinnen
F
F
Fuseau
C
C
Crouzel
C
C
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging*; D008024:Ligands; D008168:Lung / Q000000981:diagnostic imaging*; D011412:Propanolamines / Q000097:blood / Q000494:pharmacology; D052999:Quinazolinones; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis* / Q000187:drug effects; D014055:Tomography, Emission-Computed
D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D008024:Ligands; D011412:Propanolamines; D052999:Quinazolinones; D019275:Radiopharmaceuticals; D018342:Receptors, Adrenergic, beta-1; C045066:HX-CH 44BS