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Annals of Nuclear Medicine

, 23:843 | Cite as

Preparation and evaluation of 186/188Re-labeled antibody (A7) for radioimmunotherapy with rhenium(I) tricarbonyl core as a chelate site

  • Kazuma OgawaEmail author
  • Hidekazu Kawashima
  • Seigo Kinuya
  • Kazuhiro Shiba
  • Masahisa Onoguchi
  • Hiroyuki Kimura
  • Kazuyuki Hashimoto
  • Akira Odani
  • Hideo Saji
Original Article

Abstract

Objective

Rhenium is one of the most valuable elements for internal radiotherapy because 186Re and 188Re have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of 186/188Re. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the 186/188Re complex to protein after radiolabeling with the bifunctional chelating agent. These processes are complicated. Therefore, we planned the preparation by a simple method and evaluation of a stable 186/188Re-labeled antibody. For this purpose, we selected 186/188Re(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. 186/188Re-labeled A7 was prepared by directly reacting a 186/188Re(I) tricarbonyl precursor, [186/188Re(CO)3(H2O)3]+, with A7. We then compared the biodistribution of 186/188Re-labeled A7 in tumor-bearing mice with 125I-labeled A7.

Methods

For labeling A7, [186/188Re(CO)3(H2O)3]+ was prepared according to a published procedure. 186/188Re-labeled A7 (186/188Re-(CO)3-A7) was prepared by reacting [186/188Re(CO)3(H2O)3]+ with A7 at 43°C for 2 h. Biodistribution experiments were performed by the intravenous administration of 186/188Re-(CO)3-A7 solution into tumor-bearing mice.

Results

186Re-(CO)3-A7 and 188Re-(CO)3-A7 were prepared with radiochemical yields of 23 and 28%, respectively. After purification with a PD-10 column, 186/188Re-(CO)3-A7 showed a radiochemical purity of over 95%. In biodistribution experiments, 13.1 and 13.2% of the injected dose/g of 186Re-(CO)3-A7 and 188Re-(CO)3-A7, respectively, accumulated in the tumor at 24-h postinjection, and the tumor-to-blood ratios were over 2.0 at the same time point. Meanwhile, uptake of 125I-A7 in the tumor was almost the same as that of 186/188Re-(CO)3-A7 at 24-h postinjection. Blood clearances of 186/188Re-(CO)3-A7 were faster than those of 125I-A7.

Conclusion

186/188Re-labeled A7 showed high uptakes in the tumor. However, further modification of the labeling method would be necessary to improve radiochemical yields and their biodistribution.

Keywords

Rhenium Radioimmunotherapy Antibody Tricarbonyl 

References

  1. 1.
    Macklis RM. Radioimmunotherapy as a therapeutic option for non-Hodgkin’s lymphoma. Semin Radiat Oncol. 2007;17:176–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Dillman RO. Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies. Clin Exp Med. 2006;6:1–12.CrossRefPubMedGoogle Scholar
  3. 3.
    Davies AJ. Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab. Oncogene. 2007;26:3614–28.CrossRefPubMedGoogle Scholar
  4. 4.
    Jacene HA, Filice R, Kasecamp W, Wahl RL. Comparison of 90Y-ibritumomab tiuxetan and 131I-tositumomab in clinical practice. J Nucl Med. 2007;48:1767–76.CrossRefPubMedGoogle Scholar
  5. 5.
    Garmestani K, Milenic DE, Plascjak PS, Brechbiel MW. A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labeled Herceptin. Nucl Med Biol. 2002;29:599–606.CrossRefPubMedGoogle Scholar
  6. 6.
    Ogawa K, Mukai T, Asano D, Kawashima H, Kinuya S, Shiba K, et al. Therapeutic effects of a 186Re-complex-conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model. J Nucl Med. 2007;48:122–7.PubMedGoogle Scholar
  7. 7.
    Ferro-Flores G, Arteaga de Murphy C. Pharmacokinetics and dosimetry of 188Re-pharmaceuticals. Adv Drug Deliv Rev. 2008;60:1389–401.CrossRefPubMedGoogle Scholar
  8. 8.
    Knapp FF Jr, Beets AL, Guhlke S, Zamora PO, Bender H, Palmedo H, et al. Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment. Anticancer Res. 1997;17:1783–95.PubMedGoogle Scholar
  9. 9.
    Guhlke S, Beets AL, Oetjen K, Mirzadeh S, Biersack HJ, Knapp FF Jr. Simple new method for effective concentration of 188Re solutions from alumina-based 188W–188Re generator. J Nucl Med. 2000;41:1271–8.PubMedGoogle Scholar
  10. 10.
    Griffiths GL, Goldenberg DM, Knapp FF Jr, Callahan AP, Chang CH, Hansen HJ. Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies. Cancer Res. 1991;51:4594–602.PubMedGoogle Scholar
  11. 11.
    Ogawa K, Mukai T, Arano Y, Ono M, Hanaoka H, Ishino S, et al. Development of a rhenium-186-labeled MAG3-conjugated bisphosphonate for the palliation of metastatic bone pain based on the concept of bifunctional radiopharmaceuticals. Bioconjug Chem. 2005;16:751–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Kinuya S, Yokoyama K, Tega H, Hiramatsu T, Konishi S, Yamamoto W, et al. Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice. Jpn J Cancer Res. 1998;89:870–8.PubMedGoogle Scholar
  13. 13.
    Kinuya S, Yokoyama K, Kobayashi K, Motoishi S, Onoma K, Watanabe N, et al. Experimental radioimmunotherapy with 186Re–MAG3–A7 anti-colorectal cancer monoclonal antibody: comparison with 131I-counterpart. Ann Nucl Med. 2001;15:199–202.CrossRefPubMedGoogle Scholar
  14. 14.
    Visser GW, Gerretsen M, Herscheid JD, Snow GB, van Dongen G. Labeling of monoclonal antibodies with rhenium-186 using the MAG3 chelate for radioimmunotherapy of cancer: a technical protocol. J Nucl Med. 1993;34:1953–63.PubMedGoogle Scholar
  15. 15.
    Ogawa K, Mukai T, Arano Y, Otaka A, Ueda M, Uehara T, et al. Rhenium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation. Nucl Med Biol. 2006;33:513–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Kobayashi K, Motoishi S, Terunuma K, Rauf AA, Hashimoto K. Production of 186,188Re and recovery of tungsten from spent 188W/188Re generator. Radiochemistry. 2000;42:551–4.Google Scholar
  17. 17.
    Kotanagi H, Takahashi T, Masuko T, Hashimoto Y, Koyama K. A monoclonal antibody against human colon cancers. Tohoku J Exp Med. 1986;148:353–60.CrossRefPubMedGoogle Scholar
  18. 18.
    Wilbur DS, Hadley SW, Grant LM, Hylarides MD. Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab. Bioconjug Chem. 1991;2:111–6.CrossRefPubMedGoogle Scholar
  19. 19.
    He J, Liu C, Vanderheyden JL, Liu G, Dou S, Rusckowski M, et al. Radiolabelling morpholinos with 188Re tricarbonyl provides improved in vitro and in vivo stability to re-oxidation. Nucl Med Commun. 2004;25:731–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Schibli R, Schwarzbach R, Alberto R, Ortner K, Schmalle H, Dumas C, et al. Steps toward high specific activity labeling of biomolecules for therapeutic application: preparation of precursor [188Re(H2O)3(CO)3]+ and synthesis of tailor-made bifunctional ligand systems. Bioconjug Chem. 2002;13:750–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Tait JF, Smith C, Gibson DF. Development of annexin V mutants suitable for labeling with Tc(i)-carbonyl complex. Bioconjug Chem. 2002;13:1119–23.CrossRefPubMedGoogle Scholar
  22. 22.
    Park SH, Seifert S, Pietzsch HJ. Novel and efficient preparation of precursor [188Re(OH2)3(CO)3]+ for the labeling of biomolecules. Bioconjug Chem. 2006;17:223–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Chen KT, Lee TW, Lo JM. In vivo examination of 188Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer. Nucl Med Biol. 2009;36:355–61.CrossRefPubMedGoogle Scholar
  24. 24.
    Lin WY, Hsieh JF, Tsai SC, Yen TC, Wang SJ, Knapp FF Jr. A comprehensive study on the blockage of thyroid and gastric uptakes of 188Re-perrhenate in endovascular irradiation using liquid-filled balloon to prevent restenosis. Nucl Med Biol. 2000;27:83–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, Corstens FH, et al. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med. 2004;45:327–37.PubMedGoogle Scholar
  26. 26.
    Koppe MJ, Bleichrodt RP, Soede AC, Verhofstad AA, Goldenberg DM, Oyen WJ, et al. Biodistribution and therapeutic efficacy of 125/131I-, 186Re-, 88/90Y-, or 177Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin. J Nucl Med. 2004;45:1224–32.PubMedGoogle Scholar
  27. 27.
    Xia JY, Wang YX, Li GC, Yu JF, Yin DZ. Synthesis of pyridyl derivatives for the future functionalization of biomolecules labeled with the fac-[Re-188(CO)3(H2O)3]+ precursor. J Radioanal Nucl Chem. 2009;279:245–52.CrossRefGoogle Scholar
  28. 28.
    Oriuchi N, Higuchi T, Hanaoka H, Iida Y, Endo K. Current status of cancer therapy with radiolabeled monoclonal antibody. Ann Nucl Med. 2005;19:355–65.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2009

Authors and Affiliations

  • Kazuma Ogawa
    • 1
    • 2
    Email author
  • Hidekazu Kawashima
    • 3
  • Seigo Kinuya
    • 4
  • Kazuhiro Shiba
    • 2
  • Masahisa Onoguchi
    • 4
  • Hiroyuki Kimura
    • 5
  • Kazuyuki Hashimoto
    • 6
  • Akira Odani
    • 1
  • Hideo Saji
    • 5
  1. 1.Graduate School of Natural Science and TechnologyKanazawa UniversityKanazawaJapan
  2. 2.Advanced Science Research CenterKanazawa UniversityKanazawaJapan
  3. 3.Kyoto University HospitalKyotoJapan
  4. 4.Graduate School of Medical SciencesKanazawa UniversityKanazawaJapan
  5. 5.Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  6. 6.Japan Atomic Energy AgencyIbarakiJapan

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