Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 May;65(5):677–683. doi: 10.1038/bjc.1992.144

Comparison of the pharmacokinetics, biodistribution and dosimetry of monoclonal antibodies OC125, OV-TL 3, and 139H2 as IgG and F(ab')2 fragments in experimental ovarian cancer.

C F Molthoff 1, H M Pinedo 1, H M Schlüper 1, H W Nijman 1, E Boven 1
PMCID: PMC1977382  PMID: 1586596

Abstract

Monoclonal antibody (MAb) 139H2 was previously shown to localise specifically into ovarian cancer xenografts in nude mice. MAb 139H2 was compared with MAbs OC125 and OV-TL 3, all reactive with ovarian carcinomas, for the binding characteristics as IgG and F(ab')2 fragments with the use of the OVCAR-3 cell line grown in vitro and as s.c. xenografts. Immunoperoxidase staining of OVCAR-3 tissue sections with MAbs OC125 and 139H2 was heterogeneous, whereas MAb OV-TL 3 showed homogeneity. No differences in binding were observed between IgG and F(ab')2. The avidity expressed as apparent affinity constants of MAbs OC125, OV-TL 3 and 139H2 for OVAR-3 cells were 1 x 10(9) M-1, 1 x 10(9) M-1, and 1 x 10(8) M-1, while the number of antigenic determinants were 5 x 10(6), 1 x 10(6) and 7 x 10(6), respectively. In OVCAR-3 bearing nude mice the blood half-lives of the MAbs as IgG and F(ab')2 were approximately 50 h and 6 h, respectively. Maximum tumour uptake for the whole MAbs OC125, OV-TL 3, 139H2 and a control MAb 2C7 was 8.5%, 17.7%, 11.1% and 2.5% of the injected dose g-1, reached at 72 h after injection. For the respective F(ab')2 fragments, the maximum values were 5.2%, 10.0%, 5.5% and 1.9% of the injected dose g-1, reached between 6 h and 15 h. Tumour to non-tumour ratios were more favourable for the F(ab')2 fragments as compared to those for MAbs as IgG. Biodistribution in mice bearing a control tumour confirmed the specificity of tumour localisation of MAbs OC125, OV-TL 3 and 139H2. After injection of a tracer dose of 10 microCi of radiolabelled MAbs OC125, OV-TL 3 and 139H2 as IgG, tumours received 38 cGy, and 9 cGy. In our OVCAR-3 model, a ranking in efficiency in tumour localisation would indicate MAb OV-TL 3 as most favourable MAb, but cross-reactivity with subpopulations of human white blood cells might hamper its clinical use. Dosimetric data indicate a 4-fold higher radiation absorbed dose to tumours for IgG compared with F(ab')2 fragments.

Full text

PDF
677

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Badger C. C., Krohn K. A., Peterson A. V., Shulman H., Bernstein I. D. Experimental radiotherapy of murine lymphoma with 131I-labeled anti-Thy 1.1 monoclonal antibody. Cancer Res. 1985 Apr;45(4):1536–1544. [PubMed] [Google Scholar]
  2. Barneveld R. A., Tegelaers F. P., Ginns E. I., Visser P., Laanen E. A., Brady R. O., Galjaard H., Barranger J. A., Reuser A. J., Tager J. M. Monoclonal antibodies against human beta-glucocerebrosidase. Eur J Biochem. 1983 Aug 15;134(3):585–589. doi: 10.1111/j.1432-1033.1983.tb07606.x. [DOI] [PubMed] [Google Scholar]
  3. Bast R. C., Jr, Feeney M., Lazarus H., Nadler L. M., Colvin R. B., Knapp R. C. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981 Nov;68(5):1331–1337. doi: 10.1172/JCI110380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boerman O., Massuger L., Makkink K., Thomas C., Kenemans P., Poels L. Comparative in vitro binding characteristics and biodistribution in tumor-bearing athymic mice of anti-ovarian carcinoma monoclonal antibodies. Anticancer Res. 1990 Sep-Oct;10(5A):1289–1295. [PubMed] [Google Scholar]
  5. Buchegger F., Haskell C. M., Schreyer M., Scazziga B. R., Randin S., Carrel S., Mach J. P. Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983 Aug 1;158(2):413–427. doi: 10.1084/jem.158.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Buchegger F., Pèlegrin A., Delaloye B., Bischof-Delaloye A., Mach J. P. Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice. J Nucl Med. 1990 Jun;31(6):1035–1044. [PubMed] [Google Scholar]
  7. Corbett T. H., Griswold D. P., Jr, Roberts B. J., Peckham J. C., Schabel F. M., Jr Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975 Sep;35(9):2434–2439. [PubMed] [Google Scholar]
  8. Dillman R. O., Beauregard J. C., Sobol R. E., Royston I., Bartholomew R. M., Hagan P. S., Halpern S. E. Lack of radioimmunodetection and complications associated with monoclonal anticarcinoembryonic antigen antibody cross-reactivity with an antigen on circulating cells. Cancer Res. 1984 May;44(5):2213–2218. [PubMed] [Google Scholar]
  9. Haisma H. J., Hilgers J., Zurawski V. R., Jr Iodination of monoclonal antibodies for diagnosis and radiotherapy using a convenient one vial method. J Nucl Med. 1986 Dec;27(12):1890–1895. [PubMed] [Google Scholar]
  10. Hamilton T. C., Young R. C., McKoy W. M., Grotzinger K. R., Green J. A., Chu E. W., Whang-Peng J., Rogan A. M., Green W. R., Ozols R. F. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983 Nov;43(11):5379–5389. [PubMed] [Google Scholar]
  11. Hansson Y., Paulie S., Ben-Aïssa H., Rudberg U., Karlsson A., Perlmann P. Radioimmunolocalisation of bladder tumors xenotransplanted in nude mice. Anticancer Res. 1988 May-Jun;8(3):435–441. [PubMed] [Google Scholar]
  12. Hilkens J., Buijs F., Ligtenberg M. Complexity of MAM-6, an epithelial sialomucin associated with carcinomas. Cancer Res. 1989 Feb 15;49(4):786–793. [PubMed] [Google Scholar]
  13. Jain R. K. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987 Jun 15;47(12):3039–3051. [PubMed] [Google Scholar]
  14. Lamki L. M., Patt Y. Z., Rosenblum M. G., Shanken L. J., Thompson L. B., Schweighardt S. A., Frincke J. M., Murray J. L. Metastatic colorectal cancer: radioimmunoscintigraphy with a stabilized In-111-labeled F(ab')2 fragment of an anti-CEA monoclonal antibody. Radiology. 1990 Jan;174(1):147–151. doi: 10.1148/radiology.174.1.2294542. [DOI] [PubMed] [Google Scholar]
  15. Lindmo T., Boven E., Cuttitta F., Fedorko J., Bunn P. A., Jr Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1984 Aug 3;72(1):77–89. doi: 10.1016/0022-1759(84)90435-6. [DOI] [PubMed] [Google Scholar]
  16. Massuger L. F., Kenemans P., Claessens R. A., Verheijen R. H., Schijf C. P., Strijk S. P., Poels L. G., van Hoesel R. G., Corstens F. H. Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody. J Nucl Med. 1990 Nov;31(11):1802–1810. [PubMed] [Google Scholar]
  17. Molthoff C. F., Calame J. J., Pinedo H. M., Boven E. Human ovarian cancer xenografts in nude mice: characterization and analysis of antigen expression. Int J Cancer. 1991 Jan 2;47(1):72–79. doi: 10.1002/ijc.2910470114. [DOI] [PubMed] [Google Scholar]
  18. Molthoff C. F., Pinedo H. M., Schlüper H. M., Boven E. Pharmacokinetics and biodistribution of a new anti-episialin monoclonal antibody 139H2 in ovarian-cancer-bearing nude mice. Cancer Immunol Immunother. 1991;34(3):191–197. doi: 10.1007/BF01742312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moseley K. R., Battaile A., Knapp R. C., Haisma H. J. Localization of radiolabelled F(ab')2 fragments of monoclonal antibodies in nude mice bearing intraperitoneally growing human ovarian cancer xenografts. Int J Cancer. 1988 Sep 15;42(3):368–372. doi: 10.1002/ijc.2910420311. [DOI] [PubMed] [Google Scholar]
  20. Noguchi P., Wallace R., Johnson J., Earley E. M., O'Brien S., Ferrone S., Pellegrino M. A., Milstien J., Needy C., Browne W. Characterization of the WIDR: a human colon carcinoma cell line. In Vitro. 1979 Jun;15(6):401–408. doi: 10.1007/BF02618407. [DOI] [PubMed] [Google Scholar]
  21. Poels L. G., Peters D., van Megen Y., Vooijs G. P., Verheyen R. N., Willemen A., van Niekerk C. C., Jap P. H., Mungyer G., Kenemans P. Monoclonal antibody against human ovarian tumor-associated antigens. J Natl Cancer Inst. 1986 May;76(5):781–791. [PubMed] [Google Scholar]
  22. Rainsbury R. M., Ott R. J., Westwood J. H., Kalirai T. S., Coombes R. C., McCready V. R., Neville A. M., Gazet J. C. Location of metastatic breast carcinoma by a monoclonal antibody chelate labelled with indium-111. Lancet. 1983 Oct 22;2(8356):934–938. doi: 10.1016/s0140-6736(83)90452-x. [DOI] [PubMed] [Google Scholar]
  23. Taylor-Papadimitriou J., Peterson J. A., Arklie J., Burchell J., Ceriani R. L., Bodmer W. F. Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture. Int J Cancer. 1981 Jul 15;28(1):17–21. doi: 10.1002/ijc.2910280104. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES