Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography

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 (lDOPA), 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 150 MBq [ 99m Tc] TRODAT-1 were injected into normal male ICR mice through the caudal veins. For comparison, mice treated with 1-methyl-4-phenyl1,2,3,6-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.