Plastic constraint correction factor for brittle fracture in ductile-brittle transition temperature region

Hojo, Kiminobu*; Hirota, Takatoshi*; Nagoshi, Yasuto*; Fukahori, Takuya*; Shimizu, Kazuma*; Shimodaira, Masaki; Ogawa, Takuya*; Yashirodai, Kenji*; Ohata, Mitsuru*; Minami, Fumiyoshi*

Proceedings of ASME 2024 Pressure Vessels & Piping Conference (PVP 2024) (Internet), 9 Pages, 2024/07

https://doi.org/10.1115/PVP2024-123140

no abstracts in English

Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for radionuclide therapy

Ogawa, Kazuma*; Mizuno, Yoshiaki*; Washiyama, Koshin*; Shiba, Kazuhiro*; Takahashi, Naruto*; Kozaka, Takashi*; Watanabe, Shigeki; Shinohara, Atsushi*; Odani, Akira*

Nuclear Medicine and Biology, 42(11), p.875 - 879, 2015/11

https://doi.org/10.1016/j.nucmedbio.2015.07.001

Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of Re-MAG3-conjugated bisphosphonate (Re-MAG3-HBP), an agent for treatment of painful bone metastases

Ogawa, Kazuma*; Mukai, Takahiro*; Kawai, Keiichi*; Takamura, Norito*; Hanaoka, Hirofumi*; Hashimoto, Kazuyuki; Shiba, Kazuhiro*; Mori, Hirofumi*; Saji, Hideo*

European Journal of Nuclear Medicine and Molecular Imaging, 36(1), p.115 - 121, 2009/01

https://doi.org/10.1007/s00259-008-0925-8

We have developed a Re-MAG3 complex-conjugated bisphosphonate (Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of Re-MAG3-HBP because it has been reported that the concurrent administration of Tc-MAG3 and drugs with high affinity for serum protein enhanced total clearance and tissue distribution. The protein binding of Re-MAG3-HBP in a human serum albumin solution was significantly decreased by the addition of ceftriaxone. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein.

Assessment of Re chelate-conjugated bisphosphonate for the development of new radiopharmaceuticals for bones

Uehara, Tomoya*; Jin, Z. L.*; Ogawa, Kazuma*; Akizawa, Hiromichi*; Hashimoto, Kazuyuki; Nakayama, Morio*; Arano, Yasushi*

Nuclear Medicine and Biology, 34(1), p.79 - 87, 2007/01

https://doi.org/10.1016/j.nucmedbio.2006.10.001

In this study, a key factor affecting the pharmacokinetics of a chelate-conjugated BP was investigated to estimate the validity and the applicability of molecular design. Chemically inert and well-characterized [Re]CpTR-Gly was conjugated with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate and purified by HPLC to prepare [Re]CpTR-Gly-APD. Plasma stability, plasma protein binding, hydroxyapatite (HA) binding and the pharmacokinetics of [Re]CpTR-Gly-APD were compared with those of Re 1-hydroxyethylidene-1,1-diphosphonate (HEDP). The HPLC-purified [Re]CpTR-Gly-APD showed higher plasma stability, higher HA binding, higher bone accumulation and lower plasma protein binding than did Re -HEDP. Although Re -HEDP possessed HA binding and bone accumulation similar to those of [Re]CpTR-Gly-APD, the specific activity of Re -labeled BPs was found to play a crucial role in bone accumulation and blood clearance. Thus, the molecular design of chelate-conjugated BP would be useful for the development of bone-seeking radiopharmaceuticals with a variety of radionuclides by selecting chelating molecules that provide high specific activities.

Development of a Rhenium-186-labeled MAG3-conjugated bisphosphonate for the palliation of metastatic bone pain based on the concept of bifunctional radiopharmaceuticals

Ogawa, Kazuma*; Mukai, Takahiro*; Arano, Yasushi*; Ono, Masahiro*; Hanaoka, Hirofumi*; Ishino, Seigo*; Hashimoto, Kazuyuki; Nishimura, Hiroshi*; Saji, Hideo*

Bioconjugate Chemistry, 16(4), p.751 - 757, 2005/07

https://doi.org/10.1021/bc040249w

Rhenium-186-1-hydroxyethylidene-1,1-diphosphonate (Re-HEDP) has been used for the palliation of metastatic bone pain. Delayed blood clearance and high gastric uptake of radioactivity have been observed upon injection, due to the instability of Re-HEDP in vivo. In this study, on the basis of the concept of bifunctional radiopharmaceuticals, we designed a stable Re-mercaptoacetylglycylglycylglycine (MAG3) complex-conjugated bisphosphonate (Re-MAG3-HBP). After purification by HPLC, Re-MAG3-HBP was synthesized with a radiochemical purity of over 95%. In biodistribution experiments, the radioactivity level ofRe-MAG3-HBP in bone was significantly higher than that of Re-HEDP. Blood clearance of Re-MAG3-HBP was faster than that of Re-HEDP. In addition, the gastric accumulation of Re-MAG3-HBP radioactivity was lower than that of Re-HEDP. In conclusion, Re-MAG3-HBP is expected to be a useful radiopharmaceutical for the palliation of metastatic bone pain.

Synthesis and evaluation of bisphosphonate derivative labeled with Rhenium-186 using monoaminemonoamidedithiols as a chelating group

Mukai, Takahiro*; Ogawa, Kazuma*; Arano, Yasushi*; Ono, Masahiro*; Fujioka, Yasushi*; Izumo, Mishiroku; Konishi, Junji*; Saji, Hideo*

Journal of Labelled Compounds and Radiopharmaceuticals, 44(Suppl.1), p.S617 - S618, 2001/05

no abstracts in English

Control of biodistribution of Rhenium-186-MAG3-conjugated bisphosphonate using a competitive inhibitor of protein binding

Ogawa, Kazuma*; Mukai, Takahiro*; Kawai, Keiichi*; Takamura, Norito*; Hanaoka, Hirofumi*; Hashimoto, Kazuyuki; Saji, Hideo*

no journal, , 

Previously, based on the concept of bifunctional radiopharmaceuticals, we developed a highly stableRe-MAG3 complex conjugated bisphosphonate (Re-MAG3-HBP) for treatment of the painful bone metastases. We assumed that competitive inhibitors of protein binding might be useful forRe-MAG3-HBP because it has been reported that the concurrent administration between Tc-MAG3 and drugs with high protein binding affinity produced competitive displacement at the specific binding sites and enhanced total clearance and tissue distribution. In this study, the displacement effect between Re-MAG3-HBP and several protein binding inhibitors were investigated. Effects of each competitive protein binding inhibitor were examined in in vitro human serum. Bucolome, ceftriaxione and cefazolin as displacers of human serum albumin (HSA) binding site I, and ibuprofen as a displacer of HSA binding site II were added to each serum before addition of Re-MAG3-HBP. As a result of in vitro study, the free fraction rate of Re-MAG3-HBP was significantly increased by the addition of ceftriaxone. In biodistribution studies, the loading ceftriaxone enhanced the clearance of radioactivity of Re-MAG3-HBP in blood and non-target tissues without the reduction of the bone accumulation. These findings suggested that the use of a protein binding competitive inhibitor would be effective for lowering the side effects of Re-MAG3-HBP.

Preparation of Re-labeled antibody (A7) by a simple method using rhenium(I) tricarbonyl complex

Ogawa, Kazuma*; Kawashima, Hidekazu*; Kinuya, Seigo*; Yoshimoto, Mitsuyoshi*; Shiba, Kazuhiro*; Kimura, Hiroyuki*; Hashimoto, Kazuyuki; Mori, Hirofumi*; Saji, Hideo*

no journal, , 

Re is one of the most useful radionuclides for internal radiotherapy. However, there is a problem when protein such as antibody is used as a carrier of Re. The labeling method using bifunctional chelating agents require the conjugation of Re-complex to protein after radiolabeling with the bifunctional chelating agent. Then, we planned the preparation of a stable Re-labeled protein by a simple method. A7 monoclonal antibody was labeled by reacting Re(I) tricarbonyl precursor with A7 directly. Re labeled A7 was prepared with radiochemical yield of 23%. After purification, Re labeled A7 showed radiochemical purity over 98%. After 24 hours of incubation, about 93% of Re-A7 remained intact, which indicates Re-A7 is stable in vitro. In biodistribution experiment, 11.2% of the injected dose/g of Re-A7 accumulated in the tumor at 24 hours postinjection, and tumor to blood ratio was over 1.0 at the same time.