European Journal of Nuclear Medicine

, Volume 23, Issue 6, pp 631–638 | Cite as

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer — dosimetric and biokinetic aspects

  • Kalevi J. A. Kairemo
  • Hans A. Ramsay
  • Magnus Tagesson
  • Antti P. Jekunen
  • Timo K. Paavonen
  • Hilkka A. Jääskelä-Saari
  • Kristian Liewendahl
  • Kaj Ljunggren
  • Sauli Savolainen
  • Sven-Erik Strand
Original Article

Abstract

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (111In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45±0.24×10−3% ID/g in primary tumours and 0.52±0.20×l0−3% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm3. The radioactivity half-lives in the tumours were 30±7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that111In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using114m-In-labelled BLMC.

Key words

Bleomycin Indium radioisotopes Radionuclide imaging Radiation therapy Adjuvant chemotherapy Head and neck neoplasms 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. l.
    Watkinson JC, Lazarus CR, Mistry R, Shaheen OH, Maisey MN, Clarke SE. Technetium-99m(V) dimercaptosuccinic acid uptake in patients with head and neck squamous carcinoma: experience in imaging.J Nucl Med 1989; 30: 174–180.Google Scholar
  2. 2.
    Cummings CW, Larson SM, Dobie RA, Weymuller EA Jr, Rudd TG, Merello A. Assessment of cobalt-57 tagged bleomycin as a clinical aid in staging head and neck carcinoma.Laryngoscope 1981; 91: 529–537.Google Scholar
  3. 3.
    Teates CD, Preston DF, Boyd CM. Gallium-67 citrate imaging in head and neck tumors: report of co-operative group.J Nucl Med 1980; 21: 622–627.Google Scholar
  4. 4.
    Goode R, Goodwin D, Burgert P, Nelson L. Radioisotope scanning for tumors of the head and neck - experience with indium-111 and phosphorus-32.Arch Otolaryngol 1973; 97: 312–315.Google Scholar
  5. 5.
    Kairemo KJA, Hopsu EVM. Diagnosis of tumors of the parotid gland with anti-LEA immunoscintigraphy.Am J Roentgenol 1990; 154: 1259–1262.Google Scholar
  6. 6.
    Kairemo KJA, Hopsu EVM. Imaging of pharyngeal and laryngeal carcinomas with indium-111-labeled monoclonal antiCEA antibodies.Laryngoscope 1990; 100: 1077–1082.Google Scholar
  7. 7.
    Baum RP, Adams S, Kiefer J, Niesen A, Knecht A, Howaldt H-P, Hertel A, Adamietz IA, Sykes T, Boniface GR, Noujaim AA, Hot G. A novel Tc-99m labeled monoclonal antibody (174 H.64) for staging head and neck cancer by immunoSPECT.Acta Oncol 1993; 32: 747–751.Google Scholar
  8. 8.
    Barranco SC, Humphrey RM. The effects of bleomycin on survival and cell progression in Chinese hamster cells in vitro.Cancer Res 1971; 31: 1218–1223.Google Scholar
  9. 9.
    Umezawa H, Ishizuka M, Maeda K, Takeuchi T. Studies on bleomycin.Cancer 1967; 20: 891–895.Google Scholar
  10. 10.
    Shanta V, Krishnamurthi S. Combined bleomycin and radiotherapy in oral cancer.Clin Radiol 1980; 31: 617–620.Google Scholar
  11. 11.
    Fu KK, Phillips TL, Silverberg IJ, Jacobs C, Goffinet DR, Chun C, Friedman MA, Kohler M, McWhirter K, Carter SK, for the Northern California Oncology Group. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.J Clin Oncol 1987; 5:1410–1418.Google Scholar
  12. 12.
    Nieweg OE, Piers DA, Beekhuis H, Sluiter HJ, van der Wal AM, Woldring MG.57Co-bleomycin scintigraphy for the staging of lung cancer.Cancer 1989; 63: 1119–1122.Google Scholar
  13. l3.
    Merrick MV, Gunasekera SW. Some pharmacological aspects of a new radiopharmaceutical,111In-bleomycin. In:Radiopharmaceuticals and labelled compounds, vol 11. Vienna: IAEA; 1973: 183–193.Google Scholar
  14. 14.
    Hou D-Y, Hoch H, Johnston GS, Tsou KC, Jones AE, Farkas RJ, Miller EE. A new I111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice.J Surg Oncol 1984; 25: 168–175.Google Scholar
  15. 15.
    Kairemo KJA, Ramsay H, Nikula TK, Hopsu EVM, Taavitsainen MJ, Bondestam S, Hiltunen JV. A low pH In-111-bleomycin complex (BLMC), a tracer for radiochemotherapy of head and neck cancer.J Nucl Med Biol 1994; 38: 135–139.Google Scholar
  16. 16.
    Paavonen T, Renkonen R. Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules.Am J Pathol 1992; 141: 1259–1264.Google Scholar
  17. 17.
    Snyder WS, Fisher HL Jr, Ford MR, Warner GG. Estimates of absorbed fractions for monoenergetic photon sources uniformly distributed in various organs of a heterogenous phantom: MIRD Pamphlet no. 5.J Nucl Med 1969; 10 (Suppl 3): 7–52.Google Scholar
  18. 18.
    Stabin M. MIRDOSE 3, Radiation International Dose Information Center, Institute for Science and Education, P.O. Box 17, Oak Ridge, TN 37831, USAGoogle Scholar
  19. 19.
    Tagesson M, Ljungberg, M, Strand S-E. Transformation of activity distributions in quantitative SPELT to absorbed dose distributions in a radionuclide treatment planning system.J Nucl Med 1994; 35: 123.Google Scholar
  20. 20.
    Ljungberg M, Strand S-E, Tagesson M. A treatment planning system for radionuclide therapy.Eur J Nucl Med 1994; 21: S76.Google Scholar
  21. 21.
    Kairemo KJA, Ramsay HA, Paavonen T, Jääskelä-Saari HA, Tagesson M, Ljunggren K, Strand S-E. Biokinetics of indium111-bleomycin complex in head and neck cancer — implementations for radiochemotherapy.Cancer Detect Prev 1996; 20: in press.Google Scholar
  22. 22.
    Ljunggren K, Strand S-E. Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples.J Nucl Med 1990; 31: 2058–2063.Google Scholar
  23. 23.
    Crooke ST, Luft F, Broughton A, Strong J, Casson K, Einhorn L. Bleomycin serum pharmacokinetics as determined by a radioimmunoassay and a microbiologic assay in a patient with compromised renal function.Cancer 1977; 39: 1430–1434.Google Scholar
  24. 24.
    Kramer WG, Feldman S, Broughton A, Strong JE, Hall SW, Holoye PY. The pharmacokinetics of bleomycin in man.J Clin Pharmacol 1978; 18: 346–352.Google Scholar
  25. 25.
    Even-Sapir E, Bettman L, Iosilevsky G, Milshtein D, Frenkel A, Kolodny GM, Ben-Haim S, Israle O, Front D. SPECT quantitation of cobalt-57-bleomycin to predict treatment response and outcome of patients with lung cancer.J Nucl Med 1994; 35: 1129–1133.Google Scholar
  26. 26.
    Hou D-Y, Maruyama Y. Distribution of111In-bleomycin complex in small cell lung cancer cells by autoradiography.J Surg Oncol 1992; 49:93–97.Google Scholar
  27. 27.
    Howell RW Narra VR, Sastry KSR, Rao DV. On the equivalent dose for Auger electron emitters.Radiat Res 1993; 134: 71–78.Google Scholar
  28. 28.
    Narra VR, Sastry KSR, Goddu SM, Howell RW, Strand S-E, Rao DV The relative biological effectiveness of 99-Tc radiopharmaceuticals.Med Phys 1994; 21: 1921–1926.Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Kalevi J. A. Kairemo
    • 1
    • 3
  • Hans A. Ramsay
    • 2
  • Magnus Tagesson
    • 6
  • Antti P. Jekunen
    • 3
  • Timo K. Paavonen
    • 4
  • Hilkka A. Jääskelä-Saari
    • 2
  • Kristian Liewendahl
    • 1
  • Kaj Ljunggren
    • 6
  • Sauli Savolainen
    • 5
  • Sven-Erik Strand
    • 6
  1. 1.Department of Clinical ChemistryUniversity Central Hospital of HelsinkiFinland
  2. 2.Department of OtorhinolaryngologyUniversity Central Hospital of HelsinkiFinland
  3. 3.Department of OncologyUniversity Central Hospital of HelsinkiFinland
  4. 4.Department of PathologyUniversity of HelsinkiFinland
  5. 5.Department of PhysicsUniversity of HelsinkiFinland
  6. 6.Department of Radiation PhysicsUniversity of LundSweden

Personalised recommendations