Synthesis and enantiomeric evaluation of radiolabelled methyl phenidate for the study of dopamine reuptake sites

Simple item page
dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorMattner, Fen_AU
dc.contributor.authorMardon, Ken_AU
dc.contributor.authorDikic, Ben_AU
dc.contributor.authorPapazian, Ven_AU
dc.contributor.authorJackson, Ten_AU
dc.contributor.authorGreguric, Ien_AU
dc.date.accessioned2024-02-27T05:38:31Zen_AU
dc.date.available2024-02-27T05:38:31Zen_AU
dc.date.issued2002-04-29en_AU
dc.date.statistics2022-02-02en_AU
dc.description.abstractNeurological diseases such as Parkinson's Disease and associated Movement Disorders have been characterised by reductions in the number of dopamine re-uptake sites or dopamine transporters (DAT) on presynaptic neurons in the striatum. Radiolabelled drugs which display specific and selective binding to the DAT has thus found clinical utility in medical imaging. The psychomotor stimulant methyl phenidate (MP) or Ritalin 1 and several derivatives have demonstrated high affinity binding to these DAT where they exert their pharmacological action. MP possesses two chiral centers with its pharmacological activity being attributed to the dl-threo diastereomer, the dl-erythro being inactive. Furthermore, imaging studies using Positron Emission Tomography (PET) with carbon-11 radiolabelled MP confirmed the d-threo enantiomer to be most active. In vitro studies indicate that compounds substituted with either bromine or iodine in the 3 position of the aromatic ring exhibit high affinity and selective binding to DAT and were thus targeted for radiolabelling with both the PET tracer Bromine-76 as well as the SPECT tracer lodione-123. Threo methyl phenidate and its halogenated derivatives were prepared by the condensation of 3-bromophenylacetonitrile and 2-bromopyridine according to modified literature methods. Radiohalogenation with either 76Br or 123I was achieved by halodestannylation reactions of the corresponding tributyl stannane precursor in the presence of chloramine-T as the oxidant. Purification by C-18 reverse phase HPLC gave the dl-threo product in 70-80% radiochemical yield and in greater than 95% radiochemical purity. Separation of the d and / enantiomers was achieved by chiral HPLC. Biodistribution studies in rodents indicated high uptake of radioactivity in tissues with known DAT sites. PET and SPECT imaging studies in primates indicated high uptake in the striatum compared to the cerebellum reference tissue. The synthesis, diastereomeric separation, structure activity studies, radiolabelling and biological studies of these compounds will be presented,en_AU
dc.identifier.booktitleFrance-Australia symposium on nuclear medicine : methodology, clinical applications and pharmacology : volume of proceedingsen_AU
dc.identifier.citationKatsifis, A., Mattner, F., Mardon, K., Dikic, B., Papazian, V., Jackson, T., & Greguric, I. (2002). Synthesis and enantiomeric evaluation of radiolabelled methyl phenidate for the study of dopamine reuptake sites. Poster presented to the France-Australia symposium on nuclear medicine : methodology, clinical applications and pharmacology : volume of proceedings, Monday 29th April 2002, Sheraton on the park, Sydney, Australia. Lucas Heights, NSW : Australian Nuclear Science and Technology Organisation, (pp. 62).en_AU
dc.identifier.conferencenameFrance-Australia symposium on nuclear medicineen_AU
dc.identifier.conferenceplaceSydney, Australiaen_AU
dc.identifier.conferencestartdate2002-04-29en_AU
dc.identifier.editorsAustralian Nuclear Science and Technology Organisationen_AU
dc.identifier.pagination62en_AU
dc.identifier.placeofpublicationLucas Heights, Australiaen_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15453en_AU
dc.language.isoenen_AU
dc.publisherAustralasian Environmental Isotope Conferenceen_AU
dc.subjectAromaticsen_AU
dc.subjectCarbon 11en_AU
dc.subjectEnantiomorphsen_AU
dc.subjectIodine 123en_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectRadiopharmaceuticalsen_AU
dc.subjectSingle photon emission computed tomographyen_AU
dc.subjectSynthesisen_AU
dc.subjectBromine 76en_AU
dc.subjectDopamineen_AU
dc.subjectNervous system diseasesen_AU
dc.titleSynthesis and enantiomeric evaluation of radiolabelled methyl phenidate for the study of dopamine reuptake sitesen_AU
dc.typeConference Posteren_AU
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Nuclear medicine symposium.pdf
Size:
62.56 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.63 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Conference Publications