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To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study. We investigated two of the most commonly used PVC methods, Muller-Gartner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer’s disease (AD) PET studies of both [18F]THK5351 and [11C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbe (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data. In regions of high uptake of [18F]THK5351 and [11C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition. Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

Amyloid-β plaques and neurofibrillary tangles composed of tau protein are the neuropathological hallmarks of Alzheimer’s disease. In recent years, marked progress has been made in Alzheimer’s disease research using tau ligands for positron emission tomography (PET). However, the issue of off-target binding, that is, the binding of ligands to regions without tau pathology, remains unresolved. Tissues with melanin-containing cells (MCCs) have been suggested as binding targets for tau ligands. In the present study, we characterized the MCC-binding properties of representative tau PET ligands. Autoradiographic studies of [18F]AV-1451 and [18F]THK5351 were conducted using postmortem human midbrain sections. Saturation-binding assays of [18F]AV-1451 and [18F]THK5351 were performed with B16F10 melanoma cells. The blocking effects of 25 compounds against [18F]THK5351 binding to B16F10 cells were used to investigate the relationship between chemical structure and MCC binding. Autoradiography demonstrated specific binding of the radioligands in the substantia nigra. [18F]AV-1451 and [18F]THK5351 exhibited saturable binding to melanoma cells ([18F]AV-1451: Kd = 669 ± 196 nM, Bmax = 622 ± 269 pmol/mg protein; [18F]THK5351: Kd = 441 ± 126 nM, Bmax = 559 ± 75.5 pmol/mg protein). In blocking studies with melanoma cells, compounds bearing multiple aromatic rings and an aminopyridine group, including tau ligands such as AV-1451, PBB3, and a lead compound of MK-6240, exhibited the inhibition of [18F]THK5351 binding comparable to self-blocking by THK5351 (> 70% at 10 µM). These studies suggest that the binding properties of [18F]AV-1451 and [18F]THK5351 are sufficient to expect highlighting of tissues with a high density of MCCs. The findings of the present study should aid the development of neuroimaging ligands that do not bind to MCC.

To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study.We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [In regions of high uptake of [Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

O-[18F]fluoromethyl-L-tyrosine (18F-FMT) is a recently developed tumor-detecting agent with simple preparation and high radiochemical yields. The aim of this study was to assess the potency of 18F-FMT for differentiating tumor and inflammatory tissues using an animal model with an implanted tumor and experimentally induced inflammatory foci.An ascites hepatoma cell line, AH109A, turpentine oil and Staphylococcus aureus were inoculated subcutaneously into Donryu rats as a tumor model, aseptic inflammation model and bacterial infection model, respectively. The biodistribution of radioactivity was assessed in rats at 5, 10, 30, 60, and 120 min after injection with 18F-FMT. Dual tracer whole-body and macro autoradiographies were performed 60 min after injection with a mixture of 18F-FMT and 2-deoxy-D-[1-14C]glucose (14C-DG).Tumor uptake of 18F-FMT was on average 1.27% injected dose per gram of tissue (%ID/g) and 1.43% ID/g at 30 min and 60 min, respectively and significantly higher than that in other normal tissues, except the pancreas (3.48% ID/g at 60 min). The uptakes in the aseptic and bacterial inflammatory tissues were very low and were not different from those of the background tissues. Dual tracer whole-body and macro autoradiographic studies showed that tumor uptake of 18F-FMT was clearly higher than uptake by the other tissues, while 18F-FMT accumulated much less both in aseptic and bacterial inflammatory tissues. In contrast, the 14C-DG images showed high accumulations not only in tumors but also in aseptic and bacterial inflammatory tissues.18F-FMT seems to be a promissing tracer for the differentiation between tumor and inflammation because of higher specificity to tumor.

Three-dimensional stereotactic surface projection (3D-SSP) analyses have been widely used in dementia imaging studies. However, 3D-SSP sometimes shows paradoxical results on amyloid positron emission tomography (PET) analyses. This is thought to be caused by errors in anatomical standardization (AS) based on an (18)F-fluorodeoxyglucose (FDG) template. We developed a new method of 3D-SSP analysis for amyloid PET imaging, and used it to analyze (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) PET images of subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD).The subjects were 20 with MCI, 19 patients with AD, and 17 healthy controls. Twelve subjects with MCI were followed up for 3 years or more, and conversion to AD was seen in 6 cases. All subjects underwent PET with both FDG and BF-227. For AS and 3D-SSP analyses of PET data, Neurostat (University of Washington, WA, USA) was used. Method 1 involves AS for BF-227 images using an FDG template. In this study, we developed a new method (Method 2) for AS: First, an FDG image was subjected to AS using an FDG template. Then, the BF-227 image of the same patient was registered to the FDG image, and AS was performed using the transformation parameters calculated for AS of the corresponding FDG images. Regional values were normalized by the average value obtained at the cerebellum and values were calculated for the frontal, parietal, temporal, and occipital lobes. For statistical comparison of the 3 groups, we applied one-way analysis of variance followed by the Bonferroni post hoc test. For statistical comparison between converters and non-converters, the t test was applied. Statistical significance was defined as p0.05.Among the 56 cases we studied, Method 1 demonstrated slight distortions after AS of the image in 16 cases and heavy distortions in 4 cases in which the distortions were not observed with Method 2. Both methods demonstrated that the values in AD and MCI patients were significantly higher than those in the controls, in the parietal, temporal, and occipital lobes. However, only Method 2 showed significant differences in the frontal lobes. In addition, Method 2 could demonstrate a significantly higher value in MCI-to-AD converters in the parietal and frontal lobes.Method 2 corrects AS errors that often occur when using Method 1, and has made appropriate 3D-SSP analysis of amyloid PET imaging possible. This new method of 3D-SSP analysis for BF-227 PET could prove useful for detecting differences between normal groups and AD and MCI groups, and between converters and non-converters.

18F-FRP170, 1-(2-fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, is a new hypoxia imaging agent for positron emission tomography. This compound was synthesized by18F-labeling of RP170, which was developed as a new hydrophilic 2-nitroimidazole analog. In the present study, we analyzed dynamic whole-body imaging in healthy volunteers and dynamic tumor imaging in three patients with lung cancer.Methods: Four healthy male volunteers and three lung cancer patients were enrolled in this study. Volunteers underwent dynamic whole-body scans just after injection of18F-FRP170 for about 90 min, while the lung cancer patients underwent dynamic tumor imaging for about 60 or 120 min. Data are expressed as standardized uptake values (SUV). Regions of interest were placed over images of each organ or tumor to generate time-SUV curves.Results: The series of dynamic whole-body scans showed rapid elimination of18F-FRP170 from the kidneys following elimination from the liver. Very low physiological uptake was observed above the diaphragm.18F-FRP170 uptake in the lung cancer lesion could be visualized clearly from early after injection. The changes of tumor SUV, tumor/blood ratio, or tumor/muscle ratio about 30 min after injection or later were small.Conclusions: Dynamic imaging using18F-FRP170 demonstrated rapid elimination from the kidney, suggesting the high hydrophilicity of this imaging agent. The background activity above the diaphragm was very low, and patients with lung cancer showed clear tumor uptake of18F-FRP170 early after injection.

The distribution characteristics of18F-fluoromethylcholine (18F-choline) in tumor and inflammatory tissue were compared with those of14C or3H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of18F-choline and3H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using18F-choline and14C-2DG. Whole body (WB) ARG was performed with18F-choline. Tumor uptake of18F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of18F-choline.18F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with18F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with18F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and18F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of18F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain.