Detail of "320589-77-3"

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Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4-(2-mercapto- 2-methylpropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4-(2-mercapto- 2-methylpropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats.Some chemicals with cas registry numbers like 824975-90-8 and 320589-77-3 are also used. Samnick, Samuel; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin (Department of Nuclear Medicine, Saarland University Medical Centre, Homburg D-66421, Germany). Nuclear Medicine and Biology, 31(4), 511-522 (English) 2004 Elsevier Science Inc. CODEN: NMBIEO. ISSN: 0969-8051. DOCUMENT TYPE: Journal CA Section: 8 (Radiation Biochemistry) In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the 99mTc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4-(2-mercapto- 2-methylpropylamino)-piperidine (99mTc-FBPBAT) with those of the clin. established meta-[123I]iodobenzylguanidine (123I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various a- and b-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of 99mTc-FBPBAT and 123I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 min. Radioactivity uptake after a 60-min incubation at 37°C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, 99mTc-FBPBAT showed the higher uptake, relative to 123I-MIBG, at any given cell concn. The cellular uptake of 99mTc-FBPBAT was lower at 4°C and 20°C than at 37°C. In contrast, the 123I-MIBG uptake was only slightly temp. dependent. Inhibition expts. confirmed that the cellular uptake of 123I-MIBG is mediated by the uptake-I carrier, whereas a1- and b1-adrenoceptors were predominantly involved in the uptake of 99mTc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that 99mTc-FBPBAT accumulated in myocardium after i.v. injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per g at 15 and 60 min postinjection, compared with 3.10% and 2.21% injected dose per g of tissue (%ID/g) in the expt. with 123I-MIBG, resp. Prazosin, urapidil, and metoprolol were as effective as treatment with other adrenergic drugs in lowering cardiac uptake of 99mTc-FBPBAT. Uptake redn. was more pronounced in myocardium than in other adrenergic-rich organs, including the lung, spleen, kidney, and adrenals, suggesting that the 99mTc-FBPBAT uptake in myocardium specifically reflects a high degree of a1/b1-receptor binding to cardiac adrenergic neurons. In comparison, redn. of cardiac and pulmonary uptake of 123I-MIBG was effective after pretreatment of rats with desipramine and reserpine, confirming distinct neuronal binding sites for 99mTc-FBPBAT and 123I-MIBG. 99mTc-FBPBAT was excreted via urine and to a lower degree via feces. Urine anal. 6 h p.i. revealed that more than 40% of the total excreted radioactivity was unmetabolized 99mTc-FBPBAT. In conclusion, the uptake of 99mTc-FBPBAT in rat myocardium specifically reflects binding to cardiac adrenergic neurons. The 99mTc-FBPBAT uptake appears to be predominantly mediated via the a1/b1-adrenoceptor pathway. These data indicate that 99mTc-FBPBAT, like 123I-MIBG, may be suitable for mapping cardiac adrenergic innervation by SPET, esp. for a1/b1-adrenoceptors as target in numerous heart diseases. .