Radiosynthesis of [123I]N-methyl-4-iododexetimide and [123I]N-methyl-4-iodolevetimide: In vitro and in vivo characterisation of binding to muscarinic receptors in the rat heart

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dc.contributor.authorKassiou, Men_AU
dc.contributor.authorMardon, Ken_AU
dc.contributor.authorKatsifis, AGen_AU
dc.contributor.authorNajdovski, Len_AU
dc.contributor.authorDikic, Ben_AU
dc.contributor.authorMattner, Fen_AU
dc.contributor.authorLambrecht, RMen_AU
dc.contributor.authorHicks, RJen_AU
dc.contributor.authorEu,Pen_AU
dc.contributor.authorLoc'h, Cen_AU
dc.date.accessioned2025-08-08T04:40:39Zen_AU
dc.date.available2025-08-08T04:40:39Zen_AU
dc.date.issued1996-02en_AU
dc.date.statistics2025-08-08en_AU
dc.description.abstract[123I]N-methyl-4-iododexetimide, [123I]MIDEX, and its pharmacologically inactive enantiomer [123I]N-methyl-4-iodolevetimide, [123I]MILEV were prepared via electrophilic iododesilylation using Chloramine-T as oxidising agent followed by N-methylation using methyl iodide. The radiotracers were purified with semi-preparative HPLC with radiochemical yields of 80 ± 11% (n = 6). The average time of synthesis was 100 min with specific activity >2000 Ci/mmol. In vitro, the binding of [123I]MIDEX, after addition of carrier, measured on homogenates of rat atrium was Bmax = 4.5 ± 0.4 pmol/mg protein, Kd = 3.3 ± 0.2 nM while in the ventricle Bmax = 2.3 ± 0.2 pmol/mg protein, Kd = 4.0 ± 1.4 nM. In vitro, the binding of [123I]MILEV was non-specific. The in vivo biodistribution of [123I]MIDEX showed high uptake in the atrium (3.2% ID/g) and left and right ventricles (2.2, 2.5% ID/g respectively) at 5 min followed by clearance. High heart-to-lung and moderate liver-to-lung ratios were obtained during 60 min. Radioactivity in the atrium and ventricles was reduced by pre-administration of the m-AChR antagonist MQNB (1 mg/kg). Pretreatment of rats with other m-AChR ligands, pirenzapine (M1), methoctramine (M2) and 4-DAMP (M3) also resulted in reduction of [123I]MIDEX uptake with methoctramine being the most potent. [123I]MIDEX distribution in the rat heart was not significantly inhibited by pre-administration of selective adrenergic drugs. The uptake was highly stereoselective since the inactive enantiomer, [123I]MILEV, demonstrated very low myocardial retention. The stability of [123I]MIDEX was evaluated by performing a metabolite study on atrium samples which revealed unchanged radiotracer 60 min postinjection. These results suggest that [123I]MIDEX may be a useful single photon agent for in vivo imaging of myocardial m-AChR in humans with [123I]MILEV offering the potential of assessing non-specific binding of the active tracer. © 1996 Published by Elsevier Inc.en_AU
dc.identifier.citationKassiou, M., Mardon, K., Katsifis, A. G., Najdovski, L., Dikic, B., Mattner, F., Lambrecht, R. M., Hicks, R. J., Eu, P., & Loc'h, C. (1996). Radiosynthesis of [123I]N-methyl-4-iododexetimide and [123I]N-methyl-4-iodolevetimide: In vitro and in vivo characterisation of binding to muscarinic receptors in the rat heart. Nuclear Medicine and Biology, 23(2), 147-153. doi:10.1016/0969-8051(95)02045-4en_AU
dc.identifier.doi10.1016/0969-8051(95)02045-4en_AU
dc.identifier.issn0969-8051en_AU
dc.identifier.issue2en_AU
dc.identifier.journaltitleNuclear Medicine and Biologyen_AU
dc.identifier.pagination147-153en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/16395en_AU
dc.identifier.volume23en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.relation.ispartofNuclear Medicine and Biologyen_AU
dc.subjectReceptorsen_AU
dc.subjectGenesen_AU
dc.subjectChloraminesen_AU
dc.subjectRatsen_AU
dc.subjectRodentsen_AU
dc.subjectIn vivoen_AU
dc.subjectHearten_AU
dc.subjectLungsen_AU
dc.subjectLiveren_AU
dc.subjectDrugsen_AU
dc.subjectTracer techniquesen_AU
dc.titleRadiosynthesis of [123I]N-methyl-4-iododexetimide and [123I]N-methyl-4-iodolevetimide: In vitro and in vivo characterisation of binding to muscarinic receptors in the rat hearten_AU
dc.typeJournal Articleen_AU
oaire.citation.issue2en_AU
oaire.citation.volume23en_AU
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