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

Appl Radiat Isot. 2002 Jul;57(1):35-42. doi: 10.1016/s0969-8043(01)00253-6.

Abstract

A 99mTc labeled tropane derivative, [99mTc] TRODAT-1 (2beta-((N,N'-bis(2-mercaptoethyl) ethylene diamino)methyl), 3beta-(4-chlorophenyl) tropane), is a potential dopamine transporter (DAT) imaging agent for the central nervous system. To better understand the binding localization of [99mTc] 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-2beta-carbomethoxy-3beta-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [99mTc] TRODAT-1 were also included in this study. Doses of 150 MBq [99mTc] 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 [99mTc] 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 [99mTc] 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 [99mTc] 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 [99mTc] 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 [99mTc] TRODAT-1 has potential clinical use for neurological investigation, such as Parkinson's and similar diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Autoradiography
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism
  • Cocaine / analogs & derivatives*
  • Cocaine / pharmacology
  • Dopamine Agents* / pharmacokinetics
  • Humans
  • Levodopa / pharmacology
  • Male
  • Methylphenidate / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Organotechnetium Compounds* / pharmacokinetics
  • Parkinson Disease / diagnostic imaging
  • Radionuclide Imaging
  • Radiopharmaceuticals* / pharmacokinetics
  • Tissue Distribution
  • Tropanes* / pharmacokinetics

Substances

  • Dopamine Agents
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Tropanes
  • technetium Tc 99m TRODAT-1
  • Methylphenidate
  • Levodopa
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Cocaine