RESUMEN
Ramelteon (TAK-375) is a novel melatonin receptor agonist that is used for clinical treatment of insomnia. The present report describes radiolabeling of ramelteon with the short-lived positron-emitter ¹¹C (T(1/2)=20.4 min) by 2 methods. One method was [¹¹C]methylation of an acetoamide precursor and the other was [¹¹C]acylation of the corresponding amine precursor. First, [¹¹C]methylation method showed the low reproducibility together with the production of many kinds of side products from which the [¹¹C-methyl]Ramelteon was separated with chemical purity of <28% and radiochemical purity of >98%. Whereas, the [¹¹C]acylation method showed high efficiency and reproducibility with a good radiochemical yield (22-43%, decay corrected), high chemical and radiochemical purities (>99% each), and high specific activity (43-162 GBq/µmol) (n=5) after HPLC purification. [¹¹C]Ramelteon is a potential positron emission tomography (PET) probe for imaging the melatonin receptor.
Asunto(s)
Indenos/síntesis química , Tomografía de Emisión de Positrones/métodos , Radiofármacos/síntesis química , Receptores de Melatonina/análisis , Radioisótopos de Carbono/química , HumanosRESUMEN
BACKGROUND: The methyl-branched free fatty acid analog 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) is metabolized more rapidly than 15-(p-iodophenyl)-3(beta)-(R,S)-methylpentadecanoic acid. This study investigates whether myocardial ischemic injury to beta-oxidation and viable myocardium can be detected with the use of 9MPA in a rat myocardial ischemia model. METHODS AND RESULTS: In the acute study the left coronary arteries were occluded for 15 or 45 minutes and then reperfused; the rats were killed after 2 hours. Iodine 125 and iodine 123 9MPA was injected 60 minutes (delayed images) and 3 minutes (early images), respectively, before the rats were killed. In the subacute study the left coronary arteries were either occluded for 45 minutes and then reperfused or occluded and not reperfused. One week later, I-125 and I-123 9MPA was injected 60 minutes and 3 minutes, respectively, before the rats were killed. The distribution of 9MPA was examined with the use of dual-tracer autoradiography. In the acute study the delayed images showed a higher uptake in viable regions at risk than in normal areas and nonviable regions. In the subacute study a difference in uptake between viable regions at risk and normal areas was visible on the early images, but this difference disappeared on the delayed images. CONCLUSIONS: 9MPA is a useful tracer for detecting viable regions of ischemic myocardium during acute and subacute disease stages.