Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1

Purpose: To investigate the distributions and changes in dopamine transporters (DATs) using 99mTc-TRODAT-1 ([99mTc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8-azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane-thiolato(3-)-N2,N2\u27,S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia retina. Methods: Pigmented guinea pigs aged 3 weeks were randomly assigned into two groups: form-deprivation myopia and normal control group. The test group wore a translucent goggle covering randomly for 4 weeks, and both groups underwent biometric measurement before and after the experiment. Both Micro-single-photon emission computed tomography (SPECT) imaging and ex-vivo autoradiography were performed with the injection of 99mTc-TRODAT-1 on the 4th week for all the guinea pigs. Results: The retinas were clearly resolved with 99mTc-TRODAT-1 in both Micro-SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the normal control eyes (15.20±1.98, P=0.026, F=2.94, t=2.605), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04, P=0.003, t=5.476). In ex-vivo autoradiography, the ratio of 99mTc-TRODAT-1 uptake in the myopic retina (95.52±12.04) was 18.54±5.86 lower than in the normal control eyes (114.06±7.81, P=0.01, F=0.331, t=3.164), and was 16.95±5.78 lower than in the fellow eyes (112.47±15.67, P=0.001, t=7.179). Conclusion: 99mTc-TRODAT-1 can be used to trace the distributions and changes in DAT in the retina. DATs in the myopic retinas were lower than that in the fellow and normal control eyes. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in myopia

Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1

Purpose: To investigate the distributions and changes in dopamine transporters (DATs) using 99mTc-TRODAT-1 ([99mTc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8-azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane-thiolato(3-)-N2,N2\u27,S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia retina. Methods: Pigmented guinea pigs aged 3 weeks were randomly assigned into two groups: form-deprivation myopia and normal control group. The test group wore a translucent goggle covering randomly for 4 weeks, and both groups underwent biometric measurement before and after the experiment. Both Micro-single-photon emission computed tomography (SPECT) imaging and ex-vivo autoradiography were performed with the injection of 99mTc-TRODAT-1 on the 4th week for all the guinea pigs. Results: The retinas were clearly resolved with 99mTc-TRODAT-1 in both Micro-SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the normal control eyes (15.20±1.98, P=0.026, F=2.94, t=2.605), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04, P=0.003, t=5.476). In ex-vivo autoradiography, the ratio of 99mTc-TRODAT-1 uptake in the myopic retina (95.52±12.04) was 18.54±5.86 lower than in the normal control eyes (114.06±7.81, P=0.01, F=0.331, t=3.164), and was 16.95±5.78 lower than in the fellow eyes (112.47±15.67, P=0.001, t=7.179). Conclusion: 99mTc-TRODAT-1 can be used to trace the distributions and changes in DAT in the retina. DATs in the myopic retinas were lower than that in the fellow and normal control eyes. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in myopia

Feasibility of 99mTc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

In this paper, 99mTc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia. Pigmented guinea pigs aged 3 weeks were devided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6). The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4th week after injection of 99mTc-TRODAT-1. The retinas were clearly resolved in the images. The ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04). The results showed that 99mTc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina, and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes. Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia

Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity

Abstract Background Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function. Methods Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization. Results Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels. Conclusions Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse

Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

Myelin pathology is present in many neurological conditions such as multiple sclerosis (MS) and traumatic spinal cord injury (SCI). To facilitate development of novel therapies aimed at myelin repair, we set out to develop imaging agents that permit direct quantification of myelination in vivo. In this work, we designed and synthesized a series of fluorescent fluorinated myelin imaging agents that can be used for in vivo positron emission tomography (PET) imaging combined with subsequent post-mortem fluorescent cryoimaging. Structure–activity relationship (SAR) studies of the newly developed myelin imaging agents led us to identify a lead compound (TAFDAS, <b>21</b>) that readily enters the brain and spinal cord and selectively binds to myelin. By conducting sequential PET and 3D cryoimaging in an SCI rat model, we demonstrated for the first time that PET and cryoimaging can be combined as a novel technique to image the spinal cord with high sensitivity and spatial resolution

Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

Myelin pathology is present in many neurological conditions such as multiple sclerosis (MS) and traumatic spinal cord injury (SCI). To facilitate development of novel therapies aimed at myelin repair, we set out to develop imaging agents that permit direct quantification of myelination in vivo. In this work, we designed and synthesized a series of fluorescent fluorinated myelin imaging agents that can be used for in vivo positron emission tomography (PET) imaging combined with subsequent post-mortem fluorescent cryoimaging. Structure–activity relationship (SAR) studies of the newly developed myelin imaging agents led us to identify a lead compound (TAFDAS, <b>21</b>) that readily enters the brain and spinal cord and selectively binds to myelin. By conducting sequential PET and 3D cryoimaging in an SCI rat model, we demonstrated for the first time that PET and cryoimaging can be combined as a novel technique to image the spinal cord with high sensitivity and spatial resolution