Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography.
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.
Department of Medical Radiation Technology & Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. jjhwang@ym.edu.tw
J J
JJ
Hwang
M H
MH
Liao
T C
TC
Yen
S P
SP
Wey
K J
KJ
Lin
W H T
WH
Pan
J C
JC
Chen
G
G
Ting
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015259:Dopamine Agents / Q000493:pharmacokinetics; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014326:Tropanes / Q000493:pharmacokinetics
D015259:Dopamine Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D008774:Methylphenidate; D007980:Levodopa; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine