A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain

Journal of Medicinal Chemistry
P C MeltzerB K Madras

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.

References

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Citations

Jun 6, 2000·Advanced Drug Delivery Reviews·Y Arano
Apr 17, 1999·Bioorganic & Medicinal Chemistry Letters·P C MeltzerB K Madras
Jun 26, 1999·Nuclear Medicine and Biology·S R ChoiH F Kung
Mar 13, 2014·Nuclear Medicine and Biology·Mostafa Erfani, Mohammad Shafiei
Oct 23, 2012·Computational & Theoretical Chemistry·Dustin Wayne DemoinCarol A Deakyne
Feb 28, 2003·Seminars in Nuclear Medicine·Hank F KungSeok Rye Choi
Nov 8, 2005·Bioorganic & Medicinal Chemistry Letters·Davy M KiefferAlfons M Verbruggen
May 20, 1999·Journal of Child Neurology·L A O'TuamaG G Gascon
Jun 16, 2017·Journal of Labelled Compounds & Radiopharmaceuticals·Dionysia Papagiannopoulou
Dec 26, 2001·Chemical Reviews·S S Jurisson, J D Lydon
Sep 15, 2005·Inorganic Chemistry·Neva LazarovaJon Zubieta

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