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Development of a radioiodinated lipophilic cation as a new SPECT radiopharmaceutical for cancer diagnosis.

Research Project

Project/Area Number 13470478
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKyoto University

Principal Investigator

SAJI Hideo  Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (40115853)

Co-Investigator(Kenkyū-buntansha) KUGA Yuji  Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70321958)
MAGATA Yasuhiro  University School of Medicine, Photon Medical Research Center, Professor, 光量子医学研究センター, 教授 (20209399)
向 高弘  京都大学, 医学研究科, 助手 (30284706)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsmitochondria / membrane potentia / lipophilic cation / Rhodacyanine derivative / Radioiodine / tumor / radiopharmaceutical / ログシアニン誘導体 / 脂溶性カオチン
Research Abstract

The role of mitochondria in cancer cell phenotypes has been related with changes in cellular redox balance, cell cycle progression, protons gradients thus, large differences in mitochondrial membrane potential between carcinoma cells and normal cells occurs. Exploitation of this mitochondrial membrane potential difference has lead to the selection of a lipophilic cationic compound as a tumor-imaging agent by expecting the selective accumulation in negatively charged mitochondria in tumor cells due to the electrochemical proton gradient. In this study, we synthesized a radioiodinated rhodacyanine dye, MKT 077 derivative (IBMKT), a n electron-delocalized lipophilic cation, and evaluated its potential for cancer diagnosis.
[^<125>I]IBMKT was synthesized by a halogen-exchange reaction with the total radiochemical yield of 50% after HPLC purification. The radiochemical purity of the product was greater than 95%, and the produced [^<125>I]IBMKT was stable for at least one month after labeling. The selective accumulation into tumor cells was investigated by determining the uptake of IBMKT by six cancer cell lines. In incubation with tumor cells, [^<125>I]IBMKT was accumulated by tumor cells to a much, greater than by normal cells it accumulated 2-to 7-fold by tumor cells, as compared with that by normal cells. Furthermore, the mitochondrial membrane potential of these tumor cells was determined using radiolabeled, Rb and compared with the accumulation of [^<125>I]IBMKT by the cells. Consequently, the accumulation of [^<125>I]IBMKT by the tumor cells correlated well with the mitochondrial membrane potential of these cells. In addition, biodistribution studies in tumor-bearing mice showed higher accumulation of [^<125>I]IBMKT in tumor than those in the blood and muscle. These results indicate that this newly designed radioiodinated IBMKT seemed to hold potential for the SPECT study of tumor imaging.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Yasushi Kiyono: "A new norepinephrine transporter imaging agent for cardiac sympathetic nervous function imaging : radioiodinated(R)-N-methyl-3-(2-iodophenyl)-3-phenylpropanamine."Nucl.Med.Biol.. 30・4. 697-706 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuhiko Iida: "Development of a radioiodinated π electron-delocalized lipophilic cation as a new SPECT radiopharmaceutical for cancer diagnosis"J.Nucl.Med.. 44・5. 304-304 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Saji: "In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography."Anal.Sci.. 19・1. 67-71 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takayuki Morimoto: "Drug design of a tumor imaging agent based on mitochondrial membrane potential"Jpn.J.Nucl.Med.. 39・3. 409-409 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Saji: "Evaluation of radioiodinated 5-iodo-3-(2-(S)-azetidinylmethoxy) pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors."Ann.Nucl.Med.. 16・3. 189-200 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuhiro Magata: "Development of multi purpose synthetic system."J.Labelled Compd.Radiopharm. 44・. 1047-1049 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuhhi Kiyono, et al.: "A new norepinephrine transporter imaging agent for cardiac sympathetic nervous function imaging radioiodinated(R)-N-methyl-3-(2-iodophenyl)-3-phenylpropanamine."Nucl.Med.Biol.. 30(4). 697-706 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuhiko Iida, et al.: "Development of a radioiodinated π electron-delocalized lipophilic cation as a new SPECT radiopharmaceutical for cancer diagnosis"J.Nucl.Med. 44(5). 304-304 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Saji, et al.: "In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography."Anal.Sci.. 19(1). 67-71 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takayuki Morimoto, et al.: "Drug design of a tumor imaging agent based on mitochondrial membrane potential."Jp.J.Nucl.Med.. 39(3). 409-409 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Saji, et al.: "Evaluation of radioiodinated 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors."Ann.Nucl.Med.. 16(3). 189-200 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuhiro Magata, et al.: "Development of multi purpose synthetic system."J.Labelled Compd.Radiopharm.. 44(1). 1047-1049 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Saji: "A new norepinephrine transporter imaging agent for cardiac sympathetic nervous function imaging : radioiodinated(R)-N-methyl-3-(2-iodophenyl)-3-phenylpropanamine"Nucl.Med.Biol.. 30・4. 679-706 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideo Saji: "Development of a radioiodinated π electron-delocalized lipophilic cation as a new SPECT radiopharmaceutical for cancer diagnosis"J.Nucl.Med.. 44・5. 304-304 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideo Saji: "In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography"Anal. Sci.. 19・1. 67-71 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideo Saji: "Evaluation of radioiodinated 5-iod-3-(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors"Ann.Nucl.Med.. 16. 189-200 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayuki Morimoto: "Drug design of a tumor imaging agent based on mitochondrial membrane potential"Jpn.J.Nucl.Med.. 39(3). 409-409 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideo Saji: "Evaluation of radioiodinated 5-iodo-3-(2(S)-azetidinylmethoxy) pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors"Ann. Nucl. Med.. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hideo Saji: "Drug design of radioactive metal complexes for nuclear medical diagnosis"Biomed. Res. Trace Elements. 12(2). 141-151 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuhiro Magata: "Development of multi purpose synthetic system"J. Labelled Compd. Radiopharm.. 44. 1047-1049 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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