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220 results on '"Toyohara, Jun"'

10. Process validation and preclinical development of a new PET cerebral blood flow tracer [11C]MMP for initial clinical trials.

Author

Toyohara, Jun, Tago, Tetsuro, and Sakata, Muneyuki

Subjects
*SINGLE-photon emission computed tomography, *CEREBRAL circulation, *POSITRON emission tomography, *SIGMA receptors, *TECHNICAL specifications, *BLOOD sugar
Abstract

Background: 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is commonly used for diagnosis of dementia because brain glucose metabolism reflects neuronal activity. However, as [18F]FDG is an analogue of glucose, accumulation of tracer in the brain is affected by plasma glucose levels. In contrast, cerebral blood flow (CBF) tracers are theoretically unaffected by plasma glucose levels and are therefore expected to be useful alternatives for the diagnosis of dementia in patients with diabetes. The techniques currently used for CBF imaging using single photon emission computed tomography (SPECT) and [15O]H2O positron emission tomography (PET), but these are limited by their insufficient resolution and sensitivity for regional brain imaging, especially in patients with brain atrophy. N-isopropyl-4-[11C]methylamphetamine ([11C]MMP) is a possible CBF tracer with high resolution and sensitivity that exhibits comparable performance to that of [15O]H2O in conscious monkey brains. We performed process validation of the radiosynthesis and preclinical development of [11C]MMP prior to clinical translation. Results: The decay-corrected yields of [11C]MMP at the end of synthesis were 41.4 ± 6.5%, with 99.7 ± 0.3% radiochemical purity, and 192.3 ± 22.5 MBq/nmol molar activity. All process validation batches complied with the product specifications. The acute toxicity of MMP was evaluated at a dose of 3.55 mg/kg body weight, which is 10,000 times the potential maximum clinical dose of [11C]MMP. The acute toxicity of [11C]MMP injection at 150 or 200 times, to administer a postulated dose of 740 MBq of [11C]MMP, was also evaluated after the decay-out of 11C. No acute toxicity of MMP and [11C]MMP injection was found. No mutagenic activity was observed for MMP. The effective dose calculated according to the Medical Internal Radiation Dose (MIRD) method was 5.4 µSv/MBq, and the maximum absorbed dose to the bladder wall was 57.6 µGy/MBq. MMP, a derivative of phenylalkylamine, showed binding to the sigma receptor, but had approximately 1/100 of the affinity of existing sigma receptor imaging agents. The affinity for other brain neuroreceptors was low. Conclusions: [11C]MMP shows acceptable pharmacological safety at the dose required for adequate PET imaging. The potential risk associated with [11C]MMP PET imaging is well within the acceptable dose limit. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications.

Author

Tago, Tetsuro and Toyohara, Jun

Subjects
*PROCESS optimization, *CLINICAL medicine, *HIGH performance liquid chromatography, *RADIOCHEMICAL purification, *POSITRON emission tomography
Abstract

Background: Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general. Results: In the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%. Conclusions: Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons

Author

Ryu, Youngjae, Maekawa, Takahiro, Yoshino, Daisuke, Sakitani, Naoyoshi, Takashima, Atsushi, Inoue, Takenobu, Suzurikawa, Jun, Toyohara, Jun, Tago, Tetsuro, Makuuchi, Michiru, Fujita, Naoki, Sawada, Keisuke, Murase, Shuhei, Watanave, Masashi, Hirai, Hirokazu, Sakai, Takamasa, Yoshikawa, Yuki, Ogata, Toru, Shinohara, Masahiro, Nagao, Motoshi, and Sawada, Yasuhiro

Published
2020
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17. Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Author

Toyohara, Jun, Vugts, Danielle, Kiss, Oliver C., Todde, Sergio, Li, Xiang-Guo, Liu, Zhibo, Yang, Zhi, Gillings, Nic, Cazzola, Emiliano, Szymanski, Wiktor, Meulen, Nick van der, Reilly, Raymond, Taddei, Carlotta, Schirrmacher, Ralf, Li, Zijing, Lagebo, Yohannes Jorge, Bentaleb, Naoual, Souza Albernaz, Marta de, Lapi, Suzanne, and Ramogida, Caterina

Subjects
*RADIOCHEMISTRY, *EDITORIAL boards, *RADIOPHARMACEUTICALS, *NUCLEAR medicine, *DRUGSTORES, *READERSHIP
Abstract

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body: This selection of highlights provides commentary on 24 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects. [ABSTRACT FROM AUTHOR]

Published
2024
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33. 18F‐Fluorination of 2‐Methyl‐6‐nitrobenzenesulfonate Ester and its Application for the Synthesis of an 18F‐Labeled Amino Acid.

Author

Iida, Shogo, Tago, Tetsuro, Tada, Masatoshi, Toyohara, Jun, and Tanaka, Hiroshi

Subjects
AMINO acid synthesis, ESTERS, STERIC hindrance, AMINO acids, METHYL groups
Abstract

In the development of an efficient 18F‐labeling method for the synthesis of PET tracers, it is essential not only to improve the efficiency of [18F]fluorine incorporation into a carrier but also to minimize non‐radioactive side products from the precursor. Highly reactive sulfonate esters are promising precursors for 18F‐nucleophilic fluorination under mild conditions. However, the expected labeling efficiency from the precursor is often hampered by its competitive degradation due to coexisting bases during 18F‐fluorination. In this report, we designed a 2‐methyl‐6‐nitrobenzenesulfonate (2‐MeNs) ester as a precursor for 18F‐fluorination, in which the methyl group suppresses hydrolysis of the sulfonate ester via steric hindrance. An increase in labeling efficiency in the 18F‐labeling of a neopentyl labeling group was observed for the neopentyl 2‐MeNs ester compared with that of the 2‐nitrobenzenesulfonate ester. Ultimately, we achieved the automated synthesis of an 18F‐labeled amino acid using a neopentyl labeling group by using a 2‐MeNs ester as a precursor. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [11C]CB184 and [11C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [11C](R)-PK11195

Author

Hatano, Kentaro, Sekimata, Katsuhiko, Yamada, Takashi, Abe, Junichiro, Ito, Kengo, Ogawa, Mikako, Magata, Yasuhiro, Toyohara, Jun, Ishiwata, Kiichi, Biggio, Giovanni, Serra, Mariangela, Laquintana, Valentino, Denora, Nunzio, Latrofa, Andrea, Trapani, Giuseppe, Liso, Gaetano, Suzuki, Hiromi, Sawada, Makoto, Nomura, Masahiko, and Toyama, Hiroshi

Published
2015
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