title: A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.
abstract: The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.
authors.affiliation: Organix Inc., Woburn, Massachusetts 01801, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Meltzer
authors.forename: P
authors.initials: P
authors.lastname: Blundell
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Mahmood
authors.forename: B
authors.initials: B
authors.lastname: Garada
authors.forename: R E
authors.initials: RE
authors.lastname: Zimmerman
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: B L
authors.initials: BL
authors.lastname: Holman
authors.forename: B K
authors.initials: BK
authors.lastname: Madras
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D015394:Molecular Structure; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; C106588:technepine