TY - JOUR
T1 - Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography
AU - Hwang, J. J.
AU - Liao, M. H.
AU - Yen, T. C.
AU - Wey, S. P.
AU - Lin, K. J.
AU - Pan, W. H.T.
AU - Chen, J. C.
AU - Ting, G.
PY - 2002
Y1 - 2002
N2 - A 99mTc labeled tropane derivative, [99mTc] TRODAT-1 (2β-((N,N′-bis(2-mercaptoethyl) ethylene diamino)methyl), 3β-(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-2β-carbomethoxy-3β-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [99mTc] TRODAT-1 were also included in this study. Doses of 150MBq [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.
AB - A 99mTc labeled tropane derivative, [99mTc] TRODAT-1 (2β-((N,N′-bis(2-mercaptoethyl) ethylene diamino)methyl), 3β-(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-2β-carbomethoxy-3β-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [99mTc] TRODAT-1 were also included in this study. Doses of 150MBq [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.
KW - Dopamine transporter
KW - Macroautoradiography
KW - Parkinson's disease
KW - Striatum
KW - [Tc] TRODAT-1
UR - http://www.scopus.com/inward/record.url?scp=0035984267&partnerID=8YFLogxK
U2 - 10.1016/S0969-8043(01)00253-6
DO - 10.1016/S0969-8043(01)00253-6
M3 - 文章
C2 - 12137024
AN - SCOPUS:0035984267
SN - 0969-8043
VL - 57
SP - 35
EP - 42
JO - Applied Radiation and Isotopes
JF - Applied Radiation and Isotopes
IS - 1
ER -