[123I]-N-methyl-4iododexetimide: a radioiodinated ligand for SPECT studies of myocardial muscarinic receptors

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dc.contributor.authorKassiou, Men_AU
dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorLamnrecht, RMen_AU
dc.contributor.authorHicks, RJen_AU
dc.date.accessioned2025-10-30T00:44:57Zen_AU
dc.date.available2025-10-30T00:44:57Zen_AU
dc.date.issued1983-10-25en_AU
dc.date.statistics2025-08-08en_AU
dc.descriptionPhysical copy held by ANSTO Library at DDC: 616.07575/115.en_AU
dc.description.abstractMuscarinic cholinergic receptors (mAChR) mediate a closing in the rate of contraction of the heart and a decrease in the force of contraction, while changes in receptor density occur in various physiological, pharmacological and clinic condition. Altered muscarinic receptor distribution in the heart may be a substrate for cardiac arrhythmias and lead to cardiac arrest. Attempts to image myocardial mAChR involves use of radiotracers such as [11C]MQNB and [11C]MTRB with limited SPECT radiotracers avaliable. Recently [1231]-4-iododexetimide (I123]IDEX), a potent mAChR antagonist was used for in vivo studies of myocardial mAChR but proved unsuccessful due to its high lung uptake.‘ We are reporting the preparation and evaluation of the hydrophilic quarternized derivative: [123I]-N-methyl-4-iododexetimide (I123]MIDEX). The radiosynthesis involves firstly preparation of [123I]lDEX by electophilic iododesilylation using trifluoroacetic acid as solvent and chloramine-T as the oxidising agent as described elsewhere} followed by treatment of [123I]IDEX with excess CH3I (fig 1). The methylation reaction is carried out by dissolving [123I]IDEX (10 mCi) in tributyl phosphate (50 µL), a solvent known to promote formation of quaternary ammonium salts, followed by addition of CH3I (300 µL). The reaction mixture was tightly stoppered and heated at 90°C for 15 minutes. After evaporating the excess CH3I and cooling the mixture, isolation and purification of the radiopharmaceutical was carried out by preperative HPLC. A µ-Bondapak C18 column (300 x 7.8 mm) was used while the UV absorption was measured at 239 nm and radioactivity measured on a Berthold system. The mobile phase consisted of acetonitrile and 0.1M ammonium acetate buffer (45:55 v.v) and a flow rate of 2.5 mL/min. The retention times of [123I]IDEX and [123I]MIDEX were 38 and 26 minutes respectively. Radiochemical yields of 80% were reached while radiochemical and chemical purities assessed by HPLC were 97% and the specific activity of [123I]MIDEX was identical to [123]IDEX >2000 mCi/µmol. Rat biodistribution studies were performed and showed high heart uptake (2.4 %ID/g) 10 minutes after injection with a heart to lung radioactivity concentration ratio (H/L) of 5.1. The H/L ratio decreased rapidly to 2.2 after 30 minutes and reached unity at 60 minutes. No uptake of [123I]MIDEX was observed in the brain. The specificity and stereoselectivity of [123I]MIDEX binding at 10 minutes was demonstrated by coinjecting a cold load of levetimide (LEV 0.15 mg/kg), dexetimide (DEX 0.15 mg/kg) and methyl-quinuclidinyl benzylate (MQNB 1 mg/kg) (fig 2). With DEX and MQNB the heart uptake was reduced to 0.20 and 0.13 %1D/g displacing 92% and 95% of the activity respectively while LEV maintained high heart uptake (2.2 %ID/g). Interestingly, the kidney uptake was 21% ID/g and remained constant over a period of 30 minutes. Preliminary SPECT studies carried out on rabbit and dog will also be described. The carbon-11 methylation of dexetimide will also be mentioned. These results suggest that [mI]MIDEX has the potential of being developed as a SPECT radiotracer for the characterisation of myocardial muscarinic receptors.en_AU
dc.identifier.booktitleTenth International Symposium on Radiopharmaceutical Chemistry :abstracts under the auspice of Kyoto University (October 25-28, 1983)en_AU
dc.identifier.citationKassiou, M., Katsifis, A., Lambrecht, R. M., Eu, P., & Hicks, R. (1993). [123I]-N-methyl-4-iododexetimide: a radioiodinated ligand for SPECT studies of myocardial muscarinic receptors. Paper presented to the Tenth International Symposium on Radiopharmaceutical Chemistry, Kyoto University (October 25-28, 1983), (pp. 232-233). Kyoto, Japan : Kyoto University.en_AU
dc.identifier.conferenceenddate1983-10-28en_AU
dc.identifier.conferencenameTenth International Symposium on Radiopharmaceutical Chemistryen_AU
dc.identifier.conferenceplaceKyoto, Japanen_AU
dc.identifier.conferencestartdate1983-10-25en_AU
dc.identifier.editorsInternational Symposium on Radiopharmaceutical Chemistryen_AU
dc.identifier.pagination232-233en_AU
dc.identifier.placeofpublicationKyoto, Japanen_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/16683en_AU
dc.language.isoenen_AU
dc.publisherKyoto Universityen_AU
dc.subjectAminesen_AU
dc.subjectAnimalsen_AU
dc.subjectAcetylcholineen_AU
dc.subjectChemical preparationen_AU
dc.subjectImidesen_AU
dc.subjectIodine 123en_AU
dc.subjectLabellingen_AU
dc.subjectLigandsen_AU
dc.subjectMyocardiumen_AU
dc.subjectHearten_AU
dc.subjectOrganic iodine compoundsen_AU
dc.subjectRadiopharmaceuticalsen_AU
dc.subjectRatsen_AU
dc.subjectReceptorsen_AU
dc.subjectSingle photon emission computed tomographyen_AU
dc.subjectTissue Distributionen_AU
dc.subjectTracer techniquesen_AU
dc.subjectRadioisotopesen_AU
dc.subjectRodentsen_AU
dc.title[123I]-N-methyl-4iododexetimide: a radioiodinated ligand for SPECT studies of myocardial muscarinic receptorsen_AU
dc.typeConference Abstracten_AU
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