Abstract Introduction: Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). As a molecular imaging technique, [18F]FDG-PET imaging has provided new insight in PDAC diagnosis; however, the utility of FDG for early-stage PDAC detection remains undefined. Therefore, PET radiotracers conjugated to malignancy-specific targeting agents (e.g., antibodies targeting cancer-associated/specific antigens) have been developed to improve specificity toward cancer cells but persist in the developmental stage. One underexplored cancer cell surface-specific target is the glycocalyx. We have previously demonstrated that fucosylated glycans (H type-3 antigens) are expressed in pancreatic cancers and a recombinant lectin, rBC2LCN, binds to these glycans specifically (Shimomura O et al: Mol Cancer Ther 2018). Here, we developed a novel, lectin-based PET probe targeting cell surface glycan for pancreatic cancer. Material and Methods: The rBC2LCN (16kDa) lectin was labeled with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), prepared according to literature (Maeding P, et al: Appl Radiat Isot 2005) in phosphate buffer (pH 8.5). Obtained [18F]FB-rBC2LCN was then purified using gel filtration column (PD-10, GE, Uppsala, Sweden). A PDAC cell line, Capan-1, was used as a model which expresses H type-3 antigens. The biodistribution of the [18F]FB-rBC2LCN was evaluated in athymic nude mice bearing subcutaneous Capan-1 tumors. Static, small-animal PET imaging studies (G4, SOFIE, Dulles, VA) were performed to further evaluate in vivo tumor targeting and specificity. Results: The decay-corrected radiochemical mean yield of [18F]FB-rBC2LCN was 3.6%±0.3% (mean±SD), based on [18F]SFB, and radiochemical purity was above 95%. Cell binding and uptake revealed that [18F]FB-rBC2LCN binds to Capan-1 cells. Mice received 0.32±0.16 MBq (corresponding to 59±21 mg) of product, injected intravenously. Biodistribution studies demonstrated that Capan-1 tumor uptake (6.5±2.0 %ID/g) was high as early as 60 min after injection of [18F]FB-rBC2LCN and the uptake increased over time (9.6±2.2 and 11±3.9 at 150 and 240 min after injection, respectively). Tumor-to-muscle ratio increased with time up to 19±1.8 at 360 min after injection, indicating image contrast. Although kidneys (72±23 %ID/g), liver (7.1±1.7 %ID/g) and lungs (7.4±2.9 %ID/g) showed high uptake at 60 min after injection, the uptake of those organs decreased over time. The blood activity concentration of the tracer was also high at 60 min after injection (12±4.4 %ID/g) and decreased over time. Bone uptake was very low (below 1.8 %ID/g throughout the study), indicating that defluorinating metabolism was negligible. High-contrast PET imaging of tumors was achieved as early as 60 min after injection and the contrast became clearer over 240 min, consistent with the biodistribution result. Conclusions: Our 18F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage PDAC detection. Citation Format: Yukihito Kuroda, Tatsuya Oda, Osamu Shimomura, Bryan J. Mathis, Hiroaki Tateno, Kentaro Hatano. Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18F-labeled rBC2LCN lectin [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A016.

Mesoporous alumina spherical particles, synthesized via spray-drying with the self-assembly of EOnPOmEOn, have been utilized for the development of clinical-grade molybdenum-99/technetium-99 m (Mo-99/Tc-99m) generators. When evaluated as molybdenum (Mo) adsorbents, the mesoporous alumina spherical particles are useful for effective adsorption of Mo ions rather than commercially available particulate alumina. The effects of surfactant removal methods on the Mo adsorption property are also systematically investigated using the batch method. Batch adsorption studies reveal practical adsorption capacities ranging from 45.9 to 91.2 mg Mo g(-1) in a Mo solution (1000 mg Mo L-1) at pH 3. The experimental results indicate the following trend in Mo adsorption capacity: solvent extraction >calcination (400 degrees C and 800 degrees C) >commercially available alumina (Medical Al2O3 used as is). To explore the feasibility of developing a clinical-scale generator, a novel tandem column generator concept is employed. Using the spray-dried and extracted mesoporous alumina, Tc-99m eluted from the generator exhibits high radionuclidic, radiochemical, and chemical purity, making it suitable for the preparation of Tc-99m-labeled radiopharmaceuticals.

To investigate differences in uptake regions between methyl-11C-L-methionine positron emission tomography (11C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries. Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of 11C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by 11C-MET PET using MRI as the reference were evaluated. The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50

Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor-specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC-targeting ability of rBC2LCN lectin, combined with fluorine-18 (18 F) ([18 F]FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [18 F]N-succinimidyl-4-fluorobenzoate ([18 F]SFB) was conjugated to rBC2LCN, and [18 F]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [18 F]FB-rBC2LCN binds to H-type-3-positive Capan-1 pancreatic cancer cells. As early as 60 min after [18 F]FB-rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan-1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor-to-muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High-contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [18 F]FB-rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18 F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage pancreatic cancer detection.

In this work, the mechanisms responsible for the adsorption of molybdate ions on alumina are investigated using in-depth surface analyses of alumina specimens immersed in solutions containing different molybdate ions at different pH values. The obtained results reveal that when alumina is immersed in an acidic solution containing molybdate ions, the hydroxyl groups present on the surface are removed to generate positively charged sites, and molybdate ions (MoO42- or AlMo6O24H63-) are adsorbed via an electrostatic interaction. Alumina dissolves slightly in an acidic solution to form AlMo6O24H63-, which is more easily desorbed than MoO42-. Furthermore, the enhancement in the Mo adsorption or desorption property may be achieved by enriching the surface of the alumina adsorbent with many -OH groups and optimizing Mo solution to adsorb molybdate ions on alumina as MoO42- ions. These findings will assist researchers in engineering more efficient and stable alumina-based adsorbents for molybdenum adsorption used in medical radioisotope (Mo-99/Tc-99m) generators.

Undershot cross-flow turbines are applicable to shallow open channel flows and are characterized by a simple structure free of guide vanes or a casing. Since these water turbines operate in a free surface flow field, the optimum inlet blade angle and outlet blade angle are considered to vary with the flow rate in the open channel; however, guidelines for setting these angles are yet to be established. In this study, a method to improve the performance of an undershot cross-flow water turbine based on shock loss reduction was proposed. First, by varying the blade angle of the straight blades of the turbine, the inlet blade angle and outlet blade angle which reduced shock loss in the first-stage inlet region and second-stage inlet region were investigated through free surface flow analysis. From the results, it was shown that by taking the inlet and outlet blade angles which minimize the first-stage and second-stage shock losses for straight blades and applying them to curved blades, shock loss is reduced, thereby improving turbine efficiency and turbine output.

The activation of microglia in various brain pathologies is accompanied by an increase in the expression of peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO). However, whether activated microglia have a neuroprotective or neurotoxic effect on neurons in the brain is yet to be determined. In this study, we investigated the ability of the novel PBR/TSPO ligand FEPPA to detect activated microglia in an animal model of primary neurotoxic microglia activation. [18F] FEPPA positron emission tomography (PET) imaging was performed before and after intraperitoneal administration of lipopolysaccharide (LPS) (LPS group) or saline (control group) in a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson’s disease. Images were compared between these groups. After imaging, the brains were collected, and the activated microglia at the disease sites were analyzed by the expression of inflammatory cytokines and immunohistochemistry staining. These results were then comparatively examined with those obtained by PET imaging. In the unilateral 6-OHDA lesion rat model, the PBR/TSPO PET signal was significantly increased in the LPS group compared with the saline group. As the increased signal was observed 4 h after the injection, we considered it an acute response to brain injury. In the post-imaging pathological examination, activated microglia were found to be abundant at the site where strong signals were detected, and the expression of the inflammatory cytokines TNF-α and IL-1β was increased. Intraperitoneal LPS administration further increased the expression of inflammatory cytokines, and the PBR/TSPO PET signal increased concurrently. The increase in inflammatory cytokine expression correlated with enhanced signal intensity. PET signal enhancement by PBR/TSPO at the site of brain injury correlated with the activation of microglia and production of inflammatory cytokines. Furthermore, because FEPPA enables the detection of neurotoxic microglia on PET images, we successfully constructed a novel PET detection system that can monitor neurodegenerative diseases.

The effective utilization of various biomolecules for creating a series of mesoporous boehmite (γ-AlOOH) and gamma-alumina (γ-Al2 O3 ) nanosheets with unique hierarchical multilayered structures is demonstrated. The nature and concentration of the biomolecules strongly influence the degree of the crystallinity, the morphology, and the textural properties of the resulting γ-AlOOH and γ-Al2 O3 nanosheets, allowing for easy tuning. The hierarchical γ-AlOOH and γ-Al2 O3 multilayered nanosheets synthesized by using biomolecules exhibit enhanced crystallinity, improved particle separation, and well-defined multilayered structures compared to those obtained without biomolecules. More impressively, these γ-AlOOH and γ-Al2 O3 nanosheets possess high surface areas up to 425 and 371 m2  g-1 , respectively, due to their mesoporous nature and hierarchical multilayered structure. When employed for molybdenum adsorption toward medical radioisotope production, the hierarchical γ-Al2 O3 multilayered nanosheets exhibit Mo adsorption capacities of 33.1-40.8 mg g-1 . The Mo adsorption performance of these materials is influenced by the synergistic combination of the crystallinity, the surface area, and the pore volume. It is expected that the proposed biomolecule-assisted strategy may be expanded for the creation of other 3D mesoporous oxides in the future.

We conducted the present phase I/IIa positron emission tomography (PET) imaging study with 89Zr conjugated with desferroxamine-IAB2M (89Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer.

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with 89Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. 89Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with 89Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of 89Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using 89Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.

N,N-di-n-propyl-2-[2-(4-[11C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([11C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [11C]CB184 in healthy human volunteers.

Recently, small hydroelectric generators have gained attention as a further development in water turbine technology for ultra low head drops in open channels. The authors have evaluated the application of cross-flow water turbines in open channels as an undershot type after removing the casings and guide vanes to substantially simplify these water turbines. However, because undershot cross-flow water turbines are designed on the basis of cross-flow water turbine runners used in typical pipelines, it remains unclear whether the number of blades has an effect on the performance or flow fields. Thus, in this research, experiments and numerical analyses are employed to study the performance and flow fields of undershot cross-flow water turbines with varying number of blades. The findings show that the turbine output and torque are lower, the fluctuation is significantly higher, and the turbine efficiency is higher for runners with 8 blades as opposed to those with 24 blades.

We performed preclinical and first-in-man clinical positron emission tomography (PET) studies in human brain using N,N-di-n-propyl-2-[2-(4-[11C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([11C]CB184) to image the 18-kDa translocator protein (TSPO), which is overexpressed in activated microglia in neuroinflammatory conditions.

We have developed water turbines appropriately for low head open channels to effectively utilize the hydro power energy. To improve the performance of the turbine, it is necessary to determine the free surface flow patterns around the turbine. We introduced the new equipment system and the more precise computational grid of numerical analysis, it was possible to specify more precise flow patterns than old ones. Time-averaged velocity distribution at inner or outer circumference of runner was almost consistent. The flow direction at the second stage outlet had rapidly changed against the mainstream. At the inner circumference of runner at the first stage outlet, the small scale vertical flow toward the same rotational direction of runner occurred. In addition, we investigated the transient flow patterns at outer circumference of the runner.

An undershot cross-flow water turbine does not require a casing for open channels and hence considerable simplification is attained. We proved that shock loss at first-stage and second-stage inlet areas has a considerable influence on turbine performance in previous study. So, in this study, we changed the blades angle of straight turbine and investigated the effect of shock loss on its performance. Then, we changed the inlet and outlet blades angle of curved turbine appropriately and tried to performance improvement of this turbine. As a result, shock loss of curved turbine could be reduced and turbine performance was also improved. In addition, we found that flow field became better by changing inlet and outlet blades angle of curved turbine and flow field also has a considerable influence on turbine performance.

Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [11C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [11C]CB184 was evaluated as a potentially more sensitive PET tracer.

We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [11C]CB184 and [11C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [11C]CB148 and [11C](R)-PK11195.