Applied Radiation and Isotopes 57 (2002) 35–42 Biodistribution study of [ 99m Tc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography J.J. Hwang a, *, M.H. Liao b,c , T.C. Yen d , S.P. Wey b , K.J. Lin d , W.H.T. Pan c , J.C. Chen e , G. Ting b a Department of Medical Radiation Technology & Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan b Institute of Nuclear Energy Research, Lungtan, Taoyen, Taiwan c Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan d Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan e Department of Pharmacology, Chang Gung University, Taipei, Taiwan Received 30 January 2001; received in revised form 17 August 2001; accepted 4 October 2001 Abstract A 99m Tc labeled tropane derivative, [ 99m Tc] TRODAT-1 (2b-((N,N 0 -bis(2-mercaptoethyl) ethylene diamino)methyl), 3b-(4-chlorophenyl) tropane), is a potential dopamine transporter (DAT) imaging agent for the central nervous system. To better understand the binding localization of [ 99m Tc] TRODAT-1 both in the brain and the body, whole-body macroautoradiography (WBAR) was used in this study. The effect of DAT competing drugs, such as levadopa (l- DOPA), N-methyl-2b-carbomethoxy-3b-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [ 99m Tc] TRODAT-1 were also included in this study. Doses of 150MBq [ 99m Tc] TRODAT-1 were injected into normal male ICR mice through the caudal veins. For comparison, mice treated with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP), l-DOPA, methylphenidate and CFT, respectively, were also investigated under the similar protocols. One and a half hours after [ 99m Tc] TRODAT-1 injection, the mice were sacrificed. Whole-body autoradiography was performed immediately after sacrifice. Both frontal and sagittal sections showed that the liver and mucosa of stomach had the highest uptake of [ 99m Tc] TRODAT-1. Other binding sites included the periphery of the spinal cord and the epithelium of the intestine. In the brain, autoradiographic imaging obtained from frontal sections showed symmetrical uptakes of [ 99m Tc] TRODAT-1 in bilateral striata. Remaining binding sites include olfactory bulbs, thyroid gland, and salivary gland. The autoradiographic imaging obtained from sagittal sections showed a similar biodistribution. Mice treated with MPTP or l-DOPA showed no significant difference in the uptake of [ 99m Tc] TRODAT-1 in bilateral striata, as compared to those of the control. In CFT or methylphenidate-treated mice, DAT binding sites were almost completely inhibited. These data showed that [ 99m Tc] TRODAT-1 has potential clinical use for neurological investigation, such as Parkinson’s and similar diseases. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: [ 99m Tc] TRODAT-1; Striatum; Dopamine transporter; Parkinson’s disease; Macroautoradiography 1. Introduction Dopamine is one of the key neurotransmitters and is related to brain functions, including movement, emo- tion, and cognition. Dopamine transporters (DATs), *Corresponding author. Institute of Radiological Sciences, National Yang-Ming University, 155 Li-Nong Street, Section 2 Shih-Pai, Taipei, Taiwan. Tel.: +886-2-282-67064; fax: +886- 2-2820-1095. E-mail address: jjhwang@ym.edu.tw (J.J. Hwang). 0969-8043/02/$-see front matter r 2002 Elsevier Science Ltd. All rights reserved. PII:S0969-8043(01)00253-6