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2002 Fiscal Year Final Research Report Summary

DEVELOPEMENT OF RADIOIODINATED RADIOPHARMACEUTICALS FOR INTERNAL RADIATION THERAPY OF TUMOR BASED ON ITS SPECIFIC METABOLIC ACTIVITY

Research Project

Project/Area Number 12557076
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Radiation science
Research InstitutionKanazawa University (2001-2002)
宮崎医科大学 (2000)

Principal Investigator

KAWAI Keiichi  Faculty of Medicine, Kanazawa Univ., Professor, 医学部, 教授 (30204663)

Co-Investigator(Kenkyū-buntansha) NAGAMACHI Shigeki  Miyazaki Medical College, Associate Professor, 医学部附属病院, 助教授 (40180517)
UEHARA Tomoya  ibid, Assistant Professor, 大学院・薬学研究院, 助手 (10323403)
ARANO Yasushi  Graduate School of Pharmaceutical Sciences, Chiba Univ., Professor, 大学院・薬学研究院, 教授 (90151167)
Project Period (FY) 2000 – 2002
KeywordsRadioiodine / Radioipharmaceuticals / Internal radiation therapy / Metabolic activity / Melanoma / Melanin biosynthesis / Kinetics regulation / Serum protein binding
Research Abstract

The aim of this study is to develop a new radiopharmaceutical labeled with radioiodine for detection and therapy of tumors, which has affinity to a characteristic metabolism in tumor. 3-Iodo-4-hydroxyphenyl-L-cysteine (I-L-PC), as we have reported previously, was found to have an interaction for tyrosinase, an essential and rate-limiting enzyme to melanin biosynthesis. In this study, considering higher affinity for tyrosinase, we synthesized 3-iodo-4-hydroxyphenylcysteamine (I-PCA) that was an amine derivative of I-L-PC and examined biodistribution study in melanoma-bearing mice.
4-Hydroxyphenylcysteamine (4-PCA) was synthesized and radioiodinated in our laboratory. I-PCA was prepared by conventional chloramine-T method under no-carrier added condition. The biodistribution of I-PCA in B16 melanoma-bearing C57BL6 mice showed rapid blood clearance, renal excretion and low accumulation in normal tissue. The results suggested that I-PCA achieved the desired affinity for melanin formation. T … More hat is, I-PCA has high potentiality for diagnosis of malignant melanoma. Moreover, because I-PCA accumulated low in normal tissue and showed rapid clearance, it might be applied as a therapeutic radiopharmaceutical when labeled with I-131.
Approximately 70 % of I-IMP, a cerebral blood flow agent, is bound to serum protein. If the binding of radiopharmaceutical to serum protein can be inhibited by displacers with high protein binding affinity, the total clearance and tissue distribution of this tracer would be enhanced. The interaction between I-IMP and several binding displacers was evaluated to improve cerebral imaging. The free fraction rate of I-IMP was increased up to 1.2 times of control with 6MNA, a clinically available HSA site II displacer. In monkey scintigraphic study, cerebral accumulation was significantly accelerated. Indeed, 6MNA treatment increased free I-IMP in monkey serum. Since the displacement method could easily be applied to human study, the competitive displacement can control tissue distribution and kinetics of radiopharmaceuticals in clinical application. Less

  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] 長町茂樹, 川井恵一, et al.: "術後分化型甲状腺癌における^<99m>Tc-MIBIシンチグラフィの転移病巣検出能の検討-^<131>I,^<201>T1との比較-"核医学. 37. 89-98 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara T., Arano Y., et al.: "Approaches to Reduce Renal Radioactivity Levels of Antibody Fragments"Biomed. Res. Trace Elements. 12. 152-158 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arano Y.: "Chemical Design of Radioiodination Reagents for Targeted Imaging and Radiotherapy of Tumor Using Antibody Fragments as Vehicles"Forum on Iodine Utilization Repor. 3. 158-169 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Duncan J.R., Arano Y., et al.: "Nuclear Translocation of Somatostatin Analogs"J. Nucl. Med.. 42. 529-531 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N., Kawai K., et al.: "Biodistribution and Urinary Excretion of 4-Iodo-L-meta-tyrosine"J. Labelled Compd. Radiopharm.. 44. S351-S353 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N, Kawai K., et al.: "3-[^<123>I]Iodo-α-methyl-L-tyrosine as a Substrate of Human L-Type Amino Acid Transporter-1"J. Labelled Compd. Radiopharm.. 44. S354-S356 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai K., Nagamachi S., et al.: "Regulation of ^<123>I-IMP Cerebral Accumulation by Competitive Displacement of Serum Protein Binding"J. Labelled Compd. Radiopharm.. 44. S462-S464 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takamura N., Kawai K., Nagamachi S., et al.: "Potentialization Mechanism of Domino Displacement on ^<123>I-IMP Serum Protein Binding"J. Labelled Compd. Radiopharm.. 44. S465-S467 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N., Kawai K., et al.: "Technetium-99m-MAG_3 as a Transport Substrate of Rat Renal Organic Anion Transporter-1"J. Labelled Compd. Radiopharm.. 44. S627-S629 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akizawa H., Arano Y., Uehara T., et al.: "Effect of Molecular Charges on Renal Uptake of ^<111>In-DTPA-conjugated Peptides"Nucl. Med. Biol.. 28. 761-768 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagamachi S., Kawai K., et al.: "Serial Change in ^<123>I-MIBG Myocardial Scintigraphy in Non-insulin-dependent Diabetes Mellitus"Ann. Nucl. Med.. 16. 33-38 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arano Y.: "Recent Advances in 99mTc Radiopharmaceuticals"Ann. Nucl. Med.. 16. 79-93 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akizawa H., Arano Y: "Novel methods of altering pharmacokinetics in radiopharmaceutical design : metabolizable linkers and pharmacokinetics"Q. J. Nucl. Med.. 46. 206-223 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lee J.U., Uehara T., Arano Y., et al.: "Antiproliferative Activity Induced by the Somatostatin Analogue, TT-232,in Human Pancreatic Cancer Cells"Eur. J. Cancer Res.. 38. 1526-1534 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N., Kawai K., et al.: "Characterization of 3-[^<125>I]Iodo-α-methyl-L-tyrosine Transport via Human L-Type Amino Acid Transporter 1"Nucl. Med. Biol.. 30. 31-37 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N., Kawai K., et al.: "Isoform Selectivity of 3-^<125>I-iodo-a-methyl-L-tyrosine Membrane Transport in Human L-Type Amino Acid Transporters"J. Nucl. Med.. 44. 244-246 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikano N., Kawai K., et al.: "An Artificial Amino Acid 4-Iodo-L-meta-tyrosine : Biodistribution and Excretion via Kidney"J. Nucl. Med.. 44. 625-631 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishii R., Kawai K., Nagamachi S., Arano Y., et al.: "A Novel Radiopharmaceutical for Detection of Malignant Melanoma Based on Melanin Formation : 3-Iodo-4-hydroxyphenyl-Lーcystein"Nucl. Med. Commun.. 24. 575-582 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川井恵一, 長町茂樹, 他: "放射性同位元素検査技術 第5版"渡邊克司編著:南山堂. 530 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai K., Nagamachi S., et al.: "Proceedings of International Symposium on Serum Albumin and α_1-Acid Glycoprotein from Basic Sciences to Clinical Applications"Eds. Otagiri M., Sugiyama Y., Testa B., Tillement J.P.. 349 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川井恵一, 荒野 泰, 他: "新放射化学・放射性医薬品学"佐治英郎, 前田 稔, 小島周二編集:南江堂. 307 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara T., Fujioka Y., Saji H., Arano Y.: "Approaches to Reduce Renal Radioactivity Levels of Antibody Fragments."Biomed. Res. Trace Elements. 12. 152-158 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arano Y.: "Chemical Design of Radioiodination Reagents for Targeted Imaging and Radiotherapy of Tumor Using Antibody Fragments as Vehicles"Forum on Iodine Utilization Report. 3. 158-169 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Duncan J.R., Anderson C.J., Arano Y.: "Nuclear Translocation of Somatostatin Analogs."J. Nucl. Med.. 42. 529-531 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kawai K., Flores II L.G., Nishii R., Kubodera A.: "Biodistribution and Urinary Excretion of 4-Iodo-L-mefa-tyrosine."J. Labelled Compd. Radiopharm.. 44. S351-353 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kawai K.. Ishikawa N., Kubodera A.: "3-[^<123>I]Iodo-α-niethyl-L-tyrosine as a Substrate of Human L-Type Amino Acid Transporter-1."J. Labelled Compd. Radiopharm.. 44. S354-356 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawai K. Nishii R., Takamura N., Jinnouchi S., Nagamachi S., Tamura S., Arimori K., Otagiri M: "Regulation of ^<123>I-IMP cerebral accumulation by competitive displacement of serum protein binding."J. Labelled Compd. Radiopharm.. 44. S462-464 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamura N., Kawai K.. Nishii R., Jinnouchi S., Nagamachi S., Tamura S., Arimori K., Otagiri M.: "Potentialization Mechanism of Domino Displacement on ^<123>I-IMP Serum Protein Binding."J. Labelled Compd. Radiopharm.. 44. S465-467 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kawai K., Ishikawa N., Kubodera A.: "Technetium-99m-MAG_3 as a Transport Substrate of Rat Renal Organic Anion Transporter-1."J. Labelled Compd. Radiopharm.. 44. S627-629 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawai K. Takamura H., Nishii R., Jinnouchi S., Nagamachi S., Tamura S., Arimori K., Otagiri M.: "Competitive Displacement of Serum Protein Binding to Regulate Pharmacokinetics."In Serum Albumin and α_1-Acid Glycoprotein from Basic Sciences to Clinical Applications:, Eds. Otagiri M., Sugiyama Y., Testa B., Tillement J.P.. 181-192 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akizawa H., Arano Y., Mifune M., Iwado A., Saito Y., Mukai T., Uehara, T., Ono M., Fujioka Y., Ogawa K., Kiso Y., Saji H.: "Effect of Molecular Charges on Renal Uptake of ^<111>In-DTPA-conjugated Peptides."Nucl. Med. Biol.. 28. 761-768 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagamachi S., Jinnouchi S., Kurose T., Nishii R., Kawai K- Futami S., Tamura S., Matsukura S.: "Serial Change in ^<123>I-MIBG Myocardial Scintigraphy in Non-insulin-dependent Diabetes Mellitus."Ann. Nucl. Med.. 16. 33-38 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arano Y.: "Recent Advances in ^<99m>Tc Radiopharmaceuticals."Ann. Nucl. Med.. 16. 79-93 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akizawa H. and Arano Y.: "Novel Methods of Altering Pharmacokinetics in Radiopharmaceutical Design: Metabolizable Linkers and Pharmacokinetics."Q. J. Nucl. Med.. 46. 206-223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kanai Y., Kawai K.. Ishikawa N., Endo H.: "Characterization of 3-[^<125>I]Iodo-α-methyl-L-tyrosine Transport via Human L-Type Amino Acid Transporter 1."Nucl. Med. Biol.. 30. 31-37 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kanai Y., Kawai K., Inatomi J., Kim D.K., Ishikawa N., Endo H.: "Isoform Selectivity of 3-^<125>I-iodo-a-methyl-L-tyrosine Membrane Transport in Human L-Type Amino Acid Transporters."J. Nucl. Med.. 44. 244-246 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikano N., Kawai K., Flores II L.G., Nishii R., Kubota N., Ishikawa N., Kubodera A.: "An Artificial Amino Acid 4-Iodo-L-meta-tyrosine: Biodistribution and Excretion via Kidney."J. Nucl. Med.. 44. 625-631 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishii R., Kawai K.. Flores II L.G., Kataoka H., Jinnouchi S., Nagamachi S., Arano Y., Tamura S.: "A Novel Radiopharmaceutical for Detection of Malignant Melanoma Based on Melanin Formation: 3-Iodo-4-hydroxyphenyl-L-cystein."Nucl. Med. Commun.. 23. in press

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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