[en] Many animal models have been for studying neutrodegenerative diseases in humans. Among them, Parkinson's disease (PD) model in primates treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is expected to be valid and useful in the field of regenerative medicine. MPTP-treated monkeys demonstrate parkinsonian syndrome, such as tremor, dyskinesia, rigidity, immobility, caused by the degeneration of dopamine neurons at the nigrostriatal pathway. In this model, investigation of cognitive impairment that is one of the important aspects of PD could be possible. We evaluated the degeneration process of nigrostriatal dopamine neurons with positron emission tomography (PET) using unanesthetized MPTP-treated two cynomolgus monkeys (Macaca fascicularis). The tracers used were [11C]PE2I, [11C]DOPA, [11C]raclopride for monitoring dopamine transporter (DAT) densities, dopamine (DA) turnover, dopamine D2-receptor (D2R) densities, respectively. The gross behavioral observation was also performed referring to the criteria of the PD symptoms. The motor dysfunction was not clearly observed up to the cumulative doses of 3 mg/kg MPTP. This period was called 'asymptomatic period'. As a result of PET scans in the asymptomatic period, DAT densities and DA turnover had already decreased greatly, but D2R densities had not changed clearly. These findings suggest that PET imaging can delineate the dopaminergic dysfunction in vivo even in the asymptomatic period. In human study of PD, it is reported that parkinsonism is shown after great loss of dopaminergic neutrons as well as pre-synaptic dysfunction. MPTP-treated monkeys demonstrate the parkinsonian syndrome with the similar mechanism as human PD. It can be expected that PET study with MPTP-monkeys would provide important clues relevant to the underlying cause of PD and be useful for preclinical study of regenerative medicine in this disease. (author)

[en] The present study was designed to make better Parkinson model animal and evaluate the transplantation treatment with ES cell. In the first year, we irradiated left striatum of adult rats with charged carbon particles (290 MeV/nucleon, 5 mm spread-out Bragg peak, 100 Gy) for purpose of making Parkinson model rats. At 4, 8, 12 weeks after the irradiation, we performed the rotation test to methamphetamine and the autoradiography on dopamine D2 receptor and transporter using ¹¹C-raclopride and ¹¹C-PE2I to measure the effects of the irradiation. As a result, the number of rotation increased and the distributions of dopamine D2 receptor and transporter in the striatum decreased during the time after the irradiation. These results suggested that the secondary neural damage due to the vascular degeneration caused the progressive destruction of dopamine system. To make more stable Parkinson model rats, we need to use smaller collimator and develop the accurate stereotactic irradiation system in the further research. (author)

[en] The present study was designed to make a new Parkinson disease model using carbon ion beam. In this year, we irradiated right middle forebrain bundle of adult rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars which was developed in this year. In 4 weeks after the irradiation, we performed methamphetamine induced rotation test and the autoradiography measurement on dopamine transporter using [¹¹C]PE2I to assess degeneration of dopaminergic neurons in caudate putamen (Cpu). As a result, ipsilateral rotation was observed and the distributions of dopamine transporter in the striatum decreased significantly. These results are similar to those of 6-OHDA lesioned rats, and indicate validity of this model. (author)

[en] The present study was designed to make a new Parkinson disease model using carbon ion beam. We irradiated right medial forebrain bundle of adult SD rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars. Four weeks after the irradiation, behavioral test and in vitro autoradiography showed hemi-Parkinson model as well as 6-OHDA lesioned rats. Pathological examinations showed cell death, gliosis and inflammations at the irradiated area. However, no obvious alteration was observed at the surrounding normal tissue. These results indicated utility and validity of this method. (author)

[en] In radiofrequency (RF) coil design for ultra-high-field magnetic resonance (MR) imaging, short RF wavelengths present various challenges to creating a big volume coil. When imaging a human body using an ultra-high magnetic field MR imaging system (magnetic flux density of 7 Tesla or more), short wavelength may induce artifacts from dielectric effect and other factors. To overcome these problems, we developed a patch antenna array coil (PAAC), which is a coil configured as a combination of patch antennas. We prototyped this type of coil for 7T proton MR imaging, imaged a monkey brain, and confirmed the coil's utility as an RF coil for ultra-high-field MR imaging. (author)

[en] In this study, we evaluate the utility of 4-[¹⁸F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]- N-meth ylbenzamide ([¹⁸F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [¹⁸F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V_T) was detected in the cerebellum (V_T = 11.5). [¹⁸F ]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [¹⁸F ]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains. (orig.)

[en] It has been proved that connexin (Cx)43 is expressed in the left ventricle and conduction properties are improved as one of the mechanisms involved in the antiarrhythmic effect of carbon beam radiation. However, myocardial damage and denervation effects associated with irradiation are not clear. In this study, we will perform functional analysis of myocardial blood flow (inflammation) and sympathetic nerve activity after irradiation using Positron Emission Tomography (PET) '18F-FEDAC' and '18F-FMeNER-d2'. Sixteen rabbits were divided into a healthy group on a normal diet (Cont group) and a diseased group on a fatty diet (HC group), and further divided into two groups: one receiving 15 Gy of carbon beam irradiation (THIR) and the other not receiving irradiation. The number of experiments completed this year is as follows: Cont. n=2, Cont+THIR, n=4, HC, n=4, HC+THIR, n=2. In the evaluation of myocardial blood flow, there was no effect of irradiation between the irradiated and non-irradiated groups in the control and HC models. In the HC model, a decrease in washout rate was observed, although there were individual differences. In the evaluation of cardiac sympathetic nerve function, sympathetic hyperactivity was suppressed by irradiation in HC model, and the decreased washout rate was improved by irradiation. 18F-FEDAC and 18F-FMeNER-d2 provided a high-resolution image of the radiological biology-effects. (author)

[en] Phosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [${}^{11}$C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. [${}^{11}$C]MTP38 was radiosynthesized by ${}^{11}$C-cyanation of a bromo precursor with [${}^{11}$C]HCN. PET scans of rat and rhesus monkey brains and in vitro autoradiography of brain sections derived from these species were conducted with [${}^{11}$C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (V${}_T$). The non-displaceable binding potential (BP${}_{ND}$) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BP${}_{ND}$. [${}^{11}$C]MTP38 was synthesized with radiochemical purity ≥99.4% and molar activity of 38.6 ± 12.6 GBq/µmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated V${}_T$ values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm${}^3$, respectively. The cerebellar V${}_T$ value was unchanged by pretreatment with unlabeled MTP38. Striatal BP${}_{ND}$ was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill's sigmoidal function. We have provided the first successful preclinical demonstration of in vivo PDE7 imaging with a specific PET radioligand. [${}^{11}$C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.