Radiation monitoring using manned helicopter around the Nuclear Power Station in the fiscal year 2020 (Contract research)

Futemma, Akira; Sanada, Yukihisa; Ishizaki, Azusa; Kawasaki, Yoshiharu*; Iwai, Takeyuki*; Hiraga, Shogo*; Sato, Kazuhiko*; Haginoya, Masashi*; Matsunaga, Yuki*; Kikuchi, Hikaru*; et al.

JAEA-Technology 2021-029, 132 Pages, 2022/02

JAEA-Technology-2021-029.pdf:24.58MB

By the nuclear disaster of Fukushima Daiichi Nuclear Power Station (FDNPS), Tokyo Electric Power Company (TEPCO), caused by the Great East Japan Earthquake and the following tsunami on March 11, 2011, a large amount of radioactive material was released from the FDNPS. After the nuclear disaster, airborne radiation monitoring using manned helicopter has been conducted around FDNPS. The results of the airborne radiation monitoring and the evaluation for temporal change of dose rate in the fiscal 2020 were summarized in this report. Analysis considering topographical effects was applied to the result of the airborne monitoring to improve the accuracy of conventional method. In addition, technique for discriminating gamma rays from the ground and those from the airborne Rn-progenies was also utilized to evaluate their effect on airborne radiation monitoring.

Preparation and evaluation of Re-labeled antibody (A7) for radioimmunotherapy with rhenium(I) tricarbonyl core as a chelate site

Ogawa, Kazuma*; Kawashima, Hidekazu*; Kinuya, Seigo*; Shiba, Kazuhiro*; Onoguchi, Masahisa*; Kimura, Hiroyuki*; Hashimoto, Kazuyuki; Odani, Akira*; Saji, Hideo*

Annals of Nuclear Medicine, 23(10), p.843 - 848, 2009/12

https://doi.org/10.1007/s12149-009-0319-4

Rhenium is one of the most valuable elements for internal radiotherapy because Re have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of Re. Labeling methods require the complicated processes. Therefore, we planned the preparation by a simple method and evaluation of a stable Re-labeled antibody. For this purpose, we selected Re(I) tricarbonyl complex as a chelating site. A7 was used as a model protein. Re-labeled A7 was prepared by directly reacting a Re(I) tricarbonyl precursor with A7. Re-(CO)-A7 were prepared with radiochemical yields of 23-28%. After purification, Re-(CO)-A7 showed a radiochemical purity of over 95%. In biodistribution experiments, Re-labeled A7 showed high uptakes in the tumor.

Therapeutic effects of a Re-complex-conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model

Ogawa, Kazuma*; Mukai, Takahiro*; Asano, Daigo*; Kawashima, Hidekazu*; Kinuya, Seigo*; Shiba, Kazuhiro*; Hashimoto, Kazuyuki; Mori, Hirofumi*; Saji, Hideo*

Journal of Nuclear Medicine, 48(1), p.122 - 127, 2007/01

We developed a highly stable rhenium-186 (Re)-MAG3 complex-conjugated bisphosphonate, (Re-MAG3-HBP), for the treatment of painful bone metastases. This agent showed a superior biodistribution as a bone-seeking agent in normal mice when compared with Re-HEDP. In this study, we evaluated the therapeutic effects of Re-MAG3-HBP using an animal model of bone metastasis. In the rats treated with Re-HEDP, tumor growth was comparable to that in untreated rats. In contrast, when Re-MAG3-HBP was administered, tumor growth was significantly inhibited. Allodynia induced by bone metastasis was attenuated by treatment with Re-MAG3-HBP or Re-HEDP, but Re-MAG3-HBP tended to be more effective. These results indicate that Re-MAG3-HBP could be useful as a therapeutic agent for the palliation of metastatic bone pain.

Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation

Ogawa, Kazuma*; Mukai, Takahiro*; Arano, Yasushi*; Otaka, Akira*; Ueda, Masashi*; Uehara, Tomoya*; Magata, Yasuhiro*; Hashimoto, Kazuyuki; Saji, Hideo*

Nuclear Medicine and Biology, 33(4), p.513 - 520, 2006/05

https://doi.org/10.1016/j.nucmedbio.2006.03.006

To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we synthesized a bisphosphonate derivative labeled with rhenium-186 (Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure and attached a stable Re-MAMA chelate to the amino group of a 4-amino-butylidene-bisphosphonate derivative, Re-MAMA-HBP, and investigated the effect of a hydroxyl group at the central carbon of its bisphosphonate structure on the affinity for hydroxyapatite and biodistribution by conducting a comparative study with Re-MAMA-BP. Re-MAMA-HBP was prepared by a reaction with ReO and SnCl in citrate buffer after the deprotection of trityl groups of Tr-MAMA-HBP. After reversed phase HPLC, Re-MAMA-HBP had a radiochemical purity of over 95 %. Compared with Re-MAMA-BP, Re-MAMA-HBP showed a greater affinity for hydroxyapatite beads in vitro and accumulated a significantly higher level in the femur in vivo. Thus, the introduction of a hydroxyl group into Re complex-conjugated bisphosphonates would be effective in enhancing accumulation in bone. These findings provide useful information on the design of bone-seeking therapeutic radiopharmaceuticals.

Design of a radiopharmaceutical for the palliation of painful bone metastases; Rhenium-186-labeled bisphosphonate derivative

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

Journal of Labelled Compounds and Radiopharmaceuticals, 47(11), p.753 - 761, 2004/11

https://doi.org/10.1002/jlcr.864

no abstracts in English

Labeling with radioactive rhenium for the purpose of the pain relief of cancerous bone metastasis

Ogawa, Kazuma*; Ono, Masahiro*; Fujioka, Yasushi*; Saji, Hideo*; Mukai, Takahiro*; Konishi, Junji*; Uehara, Tomoya*; Arano, Yasushi*; Onoma, Katsuyuki

Kaku Igaku, 37(5), P. 577, 2000/09

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 for Re-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.