99mTc-mazindol: a potential radiopharmaceutical agent for dopamine transporter imaging with SPECT: preparation and preliminary clinical observations

Mazindol, is clinically employed as an appetite suppressant by inhibiting neuronal dopamine (DA), norepinephrine (NE) and serotonin transporters in the brain. The aim of our study was to evaluate the possibilities of labeling Mazindol with 99mTc as a potential radiopharmaceutical agent for dopamine imaging with single photon emission computed tomography (SPECT). Materials and methods: Mazindol-dithiocarbamate, was prepared by reacting Mazindol with carbon disulfide followed by sodium hydroxide. Mazindol-dithiocarbamate, was labeled with 40 Mci of freshly eluted 99mTc, by an indirect methods. We studied 2 volunteers (n=2; between 35-60 years old) and 3 patients (n=3;between 75-80 years old). All SPECT examinations were performed on a dual-head gamma camera with a low energy all-purposed collimator. SPECT images were acquired for 28 min according to routine brain SPECT protocol at 30-60 min. after the i.v. injection of 952 MBq(25 mCi ) of Tc99m-Mazindol. Brain SPECT images with 99mTc-Mazindol and 99mTc-ECD (n=3) were compared within subjects. For each scan three consecutive coronal slices including the striatum (caudate and putamen) were summed. On this image irregular equally sized ROIs were place over striatum and frontal cortex (FC). The striatal presinaptic binding was measured semi-quantitatively by calculating striatum to CF 99mTc-Mazindol uptake ratio. Results: In all the subjects Tc99m-Mazindol showed uptake in the striatum, reflecting DA uptake. In contrast these uptakes were not seen in the SPECT imaging with 99mTc-ECD. The striatum / FC 99mTc-Mazindol ratio for normal volunteers was 0.26 and 0.40; for patients with cognitive disorder 0.21 and 0.40 and for the patients with Parkinson's disease of 0.17.There were no side effects of the radiotracer observed in any of the subjects. Conclusions: we propose 99mTc-Mazindol as a new SPECT radioligand agent for imaging the concentration of Dopamine Transporter in the striatum. 99mTc-Mazindol should be considered as useful agent for routine brain SPECT since it can be labeled by a simple and practical method. Key words: SPECT imaging; 99mTc-Mazindol; dopamine transporter (Au)