[18F]SMBT-1 is a selective and reversible monoamine oxidase B (MAO-B) radiotracer used for astrogliosis imaging. This study aimed to observe the whole-body biodistribution of [¹⁸F]SMBT-1 and evaluate peripheral MAO-B expression in healthy human volunteers using dynamic positron emission tomography (PET) imaging. Six healthy subjects (four males, two females; age range: 21–63 years) underwent nine dynamic PET scans over 5.5 h after [18F]SMBT-1 injection. The first five emission scans were acquired consecutively in a single session within 30 min (min) of post-injection (p.i.). The remaining four emission scans were performed at 70–110, 150–180, 220–250, and 290–330 min p.i. Regions of interest (ROIs) were manually drawn on the co-registered PET and magnetic resonance imaging (MRI) for the selected organs to extract mean standardized uptake values (SUVmean) and generate time-activity curves (TACs). A significantly high early uptake of [18F]SMBT-1 was observed in the kidneys, liver, heart, and stomach between 5 and 30 min p.i. The kidneys showed the highest early peak at 5 min p.i. (SUVmean = 14.2 ± 3.5). The gallbladder and intestines exhibited a delayed uptake pattern, with the gallbladder SUVmean increasing substantially from 9.0 ± 4.2 at 30 min to 123.7 ± 53.4 at 330 min. No significant differences in tracer uptake patterns were observed across participants. [¹⁸F]SMBT-1 exhibited favorable reversible kinetics in the whole-body biodistribution assessment, confirming its established utility for imaging reactive astrocytes and indicating its potential for future applications in systemic high MAO-B-related pathologies.

Objective. Prompt gamma photon, prompt x-ray, and induced positron imaging are possible methods for observing a proton beam's shape from outside the subject. However, since these three types of images have not been measured simultaneously nor compared using the same subject, their advantages and disadvantages remain unknown for imaging beam shapes in therapy. To clarify these points, we developed a triple-imaging-modality system to simultaneously measure prompt gamma photons, prompt x-rays, and induced positrons during proton beam irradiation to a phantom. Approach. The developed triple-imaging-modality system consists of a gamma camera, an x-ray camera, and a dual-head positron emission tomography (PET) system. During 80 MeV proton beam irradiation to a polymethyl methacrylate (PMMA) phantom, imaging of prompt gamma photons was conducted by the developed gamma camera from one side of the phantom. Imaging of prompt x-rays was conducted by the developed x-ray camera from the other side. Induced positrons were measured by the developed dual-head PET system set on the upper and lower sides of the phantom. Main results. With the proposed triple-imaging-modality system, we could simultaneously image the prompt gamma photons and prompt x-rays during proton beam irradiation. Induced positron distributions could be measured after the irradiation by the PET system and the gamma camera. Among these imaging modalities, image quality was the best for the induced positrons measured by PET. The estimated ranges were actually similar to those imaged with prompt gamma photons, prompt x-rays and induced positrons measured by PET. Significance. The developed triple-imaging-modality system made possible to simultaneously measure the three different beam images. The system will contribute to increasing the data available for imaging in therapy and will contribute to better estimating the shapes or ranges of proton beam.

Objective. Prompt x-ray imaging using a low-energy x-ray camera is a promising method for observing a proton beam's shape from outside the subject. Furthermore, imaging of positrons produced by nuclear reactions with protons is a possible method for observing the beam shape. However, it has not been possible to measure these two types of images with a single imaging system due to the limited imaging capability of existing systems. Imaging of both prompt x-rays and the distribution of positrons may compensate for the shortcomings of each method. Approach. We conducted imaging of the prompt x-ray using a pinhole x-ray camera during irradiation with protons in list mode. Then, after irradiation with protons, imaging of annihilation radiations from the produced positrons was conducted using the same pinhole x-ray camera in list mode. After this imaging, list-mode data were sorted to obtain prompt x-ray images and positron images. Main results. With the proposed procedure, we could measure both prompt x-ray images and induced positron images with a single irradiation by a proton beam. From the prompt x-ray images, ranges and widths of the proton beams could be estimated. The distributions of positrons were slightly wider than those of the prompt x-rays. From the time sequential positron images, we could derive the time activity curves of the produced positrons. Significance. Hybrid imaging of prompt x-rays and induced positrons using a pinhole x-ray camera was achieved. The proposed procedure would be useful for measuring prompt x-ray images during irradiation to estimate the beam structures as well as for measuring the induced positron images after irradiation to estimate the distributions and time activity curves of the induced positrons.

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications.

Proton irradiations are highly sensitive to spatial variations, mainly due to their high linear energy transfer (LET) and densely ionizing nature. In realistic clinical applications, the targets of ionizing radiation are inhomogeneous in terms of geometry and chemical composition (i.e., organs in the human body). One of the main methods for proton range monitoring is to utilize the production of proton induced positron emitting radionuclides; these could be measured precisely with positron emission tomography (PET) systems. One main positron emitting radionuclide that could be used for proton range monitoring and verification was found to be 13N that produces a peak close to the Bragg peak. In the present work, we have employed the Monte Carlo method and Spectral Analysis (SA) technique to investigate the feasibility of utilizing the 13N peak for proton range monitoring and verification in inhomogeneous targets. Two different phantom types, namely, (1) ordinary slab and (2) MIRD anthropomorphic phantoms, were used. We have found that the generated 13N peak in such highly inhomogeneous targets (ordinary slab and human phantom) is close to the actual Bragg peak, when irradiated by incident proton beam. The feasibility of using the SA technique to estimate the distribution of positron emitter was also investigated. The current findings and the developed tools in the present work would be helpful in proton range monitoring and verification in realistic clinical radiation therapy using proton beams.

Functional near infrared spectroscopy (NIRS) is the optical imaging that measures changes of blood hemodynamic while positron emission tomography (PET) measure physiological condition of the interest area.NIRS has high temporal resolution while PET image has better spatial resolution compared, however, NIRS measures hemodynamic changes in the cortex region but not in deeper brain structures.Therefore, this study is aimed to register the both image; the NIRS data on the PET image.The registration of NIRS on PET image was done on eleven subjects which undergoes NIRS and PET scan separately.To register the NIRS probe on the PET image, we did a transformation of NIRS probe coordinate to the PET coordinate based on Polaris marker position attached to the NIRS cap.The coordinate of these markers is obtained using the optical tracking system, Polaris.The resulting image forms PET and NIRS were visually aligned as well as the coordinate of the marker obtained during the PET acquisition.The probe was registered on the PET image using the in-house software.The registration done in this study is considered successful as we can view the NIRS activation area on PET image.

Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.

Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET). Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

Objective Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car‐driving have been investigated. This has not been investigated for levocetirizine, a new‐generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects. Methods In this double‐blind, placebo‐controlled, four‐way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed. Results The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer‐generation antihistamines in a manner that corresponds with subjective sedation. Conclusions Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car‐driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.

Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, 18F-THK5351, through compound optimization of arylquinoline derivatives. Methods: The in vitro binding properties, pharmacokinetics, and safety of 18F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. Results: 18F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did 18F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, 18F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than18F-THK5117. Conclusion: 18F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [18F]THK-5117 as a highly selective tau imaging radiotracer.

The biodistribution and radiation dosimetry of the 18F-labelled amyloid imaging probe ([18F] FACT) was investigated in humans.

In this report, PEM scanner using a Pr:LuAG scintillator crystal will be discussed. We have developed the PEM scanner with planer detectors which can change the angle and the distance depending on the condition of diagnosis. The planer detectors were composed of four units respectively and one unit consisted of a 20 × 64 pixels scintillator array optically coupled with three H8500 multi anode photomultipliers. As a scintillator Pr:LuAG was installed which possesses interesting properties such as a very fast decay time of 20 ns and a good energy resolution of 4.2 %. The Pr:LuAG pixel size was 2.1 mm × 2.1 mm × 15 mm and the BaSO4-type reflector was used for the array assembly. Based on this PEM system we have performed the clinical studies and compared with the images detected by the PET scanner. Because the spatial resolution of PEM is better than PET, advantages of PEM scanner were clearly shown.

A Positron Emission Mammograph (PEM) with a pair of planer detectors dedicated for breast cancer detection is developed under collaborations of Tohoku University, Kobe City Collage of Technology, and Furukawa Co., Ltd. It uses thin crystals made of a scintillator Pr:Lu3A15O12 (Pr:LuAG) of 2.1×2.1×15.0 mm in size combined with H8500 position sensitive Photo multi tubes (PMTs) from Hamamatsu. The PEM system is comprised of two opposing detectors that have 140×200 cm2 field of view (FOV). We present its basic architecture with fundamental performance, such as spatial resolution, time resolution, energy resolution, and data acquisition count rate. The Spatial resolution measured using a 22Na point sauce was found to be 1.1 mm FWHM for image planes parallel to the detector faces. Time resolution was 3.1 ns FWHM. And, energy resolution was 11.6 % FWHM (@511 keV) at the center of detector blocks. Coincident count rate was improved dramatically for optimizing energy windows level and implementation a new offset correction method.