Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Jan;63(1):37–44. doi: 10.1038/bjc.1991.9

Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG.

M Gerretsen 1, J J Quak 1, J S Suh 1, M van Walsum 1, C J Meijer 1, G B Snow 1, G A van Dongen 1
PMCID: PMC1971635  PMID: 1989663

Abstract

Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with 131I, were tested for tumour localisation and imaging in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma (HNX-HN) or from a vulva carcinoma (VX-A431). MAb IgG or F(ab')2 fragments were injected in parallel and at day 1, 2, 3 and 6 or 7, mice were either scanned with a gamma camera or dissected for determination of isotope biodistribution. In HNX-HN bearing mice, E48 IgG as well as F(ab')2 showed highly specific localisation in tumour tissue. The mean tumour uptake (n = 4) expressed as the percentage of the injected dose per gram of tumour tissue (percentage ID/g) of IgG was 11.9% at day 1 and increased to 14.6% at day 6 whereas percentage ID/g of F(ab')2 was 7.2% at day 1 and decreased during subsequent days. Tumour to blood ratios (T/B) at day 1 were 1.2 for IgG and 13.6 for F(ab')2 and reached a maximum at day 6 with values of 6.4 and 54.2 respectively. In VX-A431 bearing mice, only E48 F(ab')2 showed preferential localisation in tumour tissue. At day 1, Percentage ID/g of IgG was 3.7 and T/B was 0.3, while percentage ID/g of F(ab')2 was 2.4 and T/B was 3.2. Percentage ID/g decreased after day 1 while T/B increased. In these experiments no preferential localisation of either isotype matched 125I-labelled control IgG or F(ab')2 was observed. In F(ab')2 injected HNX-HN bearing mice as well as VX-A431 bearing mice, tumours could be visualised at day 1 and 2 without any appreciable background activity. With MAb IgG this was also possible in HNX-HN bearing mice (but not in VX-A431 bearing mice) but only at day 3 and 6. These findings suggest that the superior tumour to non-tumour ratios render the E48 F(ab')2 fragment more qualified for specific targeting of radioisotopes to tumour xenografts in this experimental setting.

Full text

PDF
37

Images in this article

39Figure 1
on p.39
39Figure 2
on p.39
41Figure 6
on p.41
42Figure 7
on p.42
42Figure 8
on p.42

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., Bernstein I. D. In vitro measurement of avidity of radioiodinated antibodies. Int J Rad Appl Instrum B. 1987;14(6):605–610. doi: 10.1016/0883-2897(87)90033-x. [DOI] [PubMed] [Google Scholar]
  2. Boeheim K., Speak J. A., Frei E., 3rd, Bernal S. D. SQM1 antibody defines a surface membrane antigen in squamous carcinoma of the head and neck. Int J Cancer. 1985 Aug 15;36(2):137–142. doi: 10.1002/ijc.2910360203. [DOI] [PubMed] [Google Scholar]
  3. Brenner B. G., Jothy S., Shuster J., Fuks A. Monoclonal antibodies to human lung tumor antigens demonstrated by immunofluorescence and immunoprecipitation. Cancer Res. 1982 Aug;42(8):3187–3192. [PubMed] [Google Scholar]
  4. Buchegger F., Mach J. P., Leonnard P., Carrel S. Selective tumor localization of radiolabeled anti-human melanoma monoclonal antibody fragment demonstrated in the nude mouse model. Cancer. 1986 Aug 1;58(3):655–662. doi: 10.1002/1097-0142(19860801)58:3<655::aid-cncr2820580310>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  5. Carey T. E., Kimmel K. A., Schwartz D. R., Richter D. E., Baker S. R., Krause C. J. Antibodies to human squamous cell carcinoma. Otolaryngol Head Neck Surg. 1983 Oct;91(5):482–491. doi: 10.1177/019459988309100503. [DOI] [PubMed] [Google Scholar]
  6. Cobb L. M. Intratumour factors influencing the access of antibody to tumour cells. Cancer Immunol Immunother. 1989;28(4):235–240. doi: 10.1007/BF00205231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colapinto E. V., Humphrey P. A., Zalutsky M. R., Groothuis D. R., Friedman H. S., de Tribolet N., Carrel S., Bigner D. D. Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res. 1988 Oct 15;48(20):5701–5707. [PubMed] [Google Scholar]
  8. Endo K., Kamma H., Ogata T. Radiolabeled monoclonal antibody 15 and its fragments for localization and imaging of xenografts of human lung cancer. J Natl Cancer Inst. 1988 Aug 3;80(11):835–842. doi: 10.1093/jnci/80.11.835. [DOI] [PubMed] [Google Scholar]
  9. Fernsten P. D., Pekny K. W., Reisfeld R. A., Walker L. E. Antigens associated with human squamous cell lung carcinoma defined by murine monoclonal antibodies. Cancer Res. 1986 Jun;46(6):2970–2977. [PubMed] [Google Scholar]
  10. 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]
  11. Hori K., Suzuki M., Abe I., Saito S. Increased tumor tissue pressure in association with the growth of rat tumors. Jpn J Cancer Res. 1986 Jan;77(1):65–73. [PubMed] [Google Scholar]
  12. Kallinowski F., Schlenger K. H., Runkel S., Kloes M., Stohrer M., Okunieff P., Vaupel P. Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts. Cancer Res. 1989 Jul 15;49(14):3759–3764. [PubMed] [Google Scholar]
  13. Kimmel K. A., Carey T. E. Altered expression in squamous carcinoma cells of an orientation restricted epithelial antigen detected by monoclonal antibody A9. Cancer Res. 1986 Jul;46(7):3614–3623. [PubMed] [Google Scholar]
  14. Koprowska I., Zipfel S., Ross A. H., Herlyn M. Development of monoclonal antibodies that recognize antigens associated with human cervical carcinoma. Acta Cytol. 1986 May-Jun;30(3):207–213. [PubMed] [Google Scholar]
  15. Kyoizumi S., Akiyama M., Kouno N., Kobuke K., Hakoda M., Jones S. L., Yamakido M. Monoclonal antibodies to human squamous cell carcinoma of the lung and their application to tumor diagnosis. Cancer Res. 1985 Jul;45(7):3274–3281. [PubMed] [Google Scholar]
  16. 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]
  17. Myoken Y., Moroyama T., Miyauchi S., Takada K., Namba M. Monoclonal antibodies against human oral squamous cell carcinoma reacting with keratin proteins. Cancer. 1987 Dec 15;60(12):2927–2937. doi: 10.1002/1097-0142(19871215)60:12<2927::aid-cncr2820601214>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  18. Quak J. J., Balm A. J., Brakkee J. G., Scheper R. J., Haisma H. J., Braakhuis B. J., Meijer C. J., Snow G. B. Localization and imaging of radiolabelled monoclonal antibody against squamous-cell carcinoma of the head and neck in tumor-bearing nude mice. Int J Cancer. 1989 Sep 15;44(3):534–538. doi: 10.1002/ijc.2910440327. [DOI] [PubMed] [Google Scholar]
  19. Quak J. J., Balm A. J., van Dongen G. A., Brakkee J. G., Scheper R. J., Snow G. B., Meijer C. J. A 22-kd surface antigen detected by monoclonal antibody E 48 is exclusively expressed in stratified squamous and transitional epithelia. Am J Pathol. 1990 Jan;136(1):191–197. [PMC free article] [PubMed] [Google Scholar]
  20. Ranken R., White C. F., Gottfried T. G., Yonkovich S. J., Blazek B. E., Moss M. S., Fee W. E., Jr, Liu Y. S. Reactivity of monoclonal antibody 17.13. with human squamous cell carcinoma and its application to tumor diagnosis. Cancer Res. 1987 Nov 1;47(21):5684–5690. [PubMed] [Google Scholar]
  21. Samuel J., Noujaim A. A., Willans D. J., Brzezinska G. S., Haines D. M., Longenecker B. M. A novel marker for basal (stem) cells of mammalian stratified squamous epithelia and squamous cell carcinomas. Cancer Res. 1989 May 1;49(9):2465–2470. [PubMed] [Google Scholar]
  22. Sands H., Jones P. L., Shah S. A., Palme D., Vessella R. L., Gallagher B. M. Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell xenografts. Cancer Res. 1988 Jan 1;48(1):188–193. [PubMed] [Google Scholar]
  23. Scheper R. J., Bulte J. W., Brakkee J. G., Quak J. J., van der Schoot E., Balm A. J., Meijer C. J., Broxterman H. J., Kuiper C. M., Lankelma J. Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance. Int J Cancer. 1988 Sep 15;42(3):389–394. doi: 10.1002/ijc.2910420314. [DOI] [PubMed] [Google Scholar]
  24. Smith T. W., Lloyd B. L., Spicer N., Haber E. Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon. Clin Exp Immunol. 1979 Jun;36(3):384–396. [PMC free article] [PubMed] [Google Scholar]
  25. Sweet M. B., Thonar E. J., Berson S. D., Skikne M. I., Immelman A. R., Kerr W. A. Biochemical studies of the matrix of craniovertebral chordoma and a metastasis. Cancer. 1979 Aug;44(2):652–660. doi: 10.1002/1097-0142(197908)44:2<652::aid-cncr2820440235>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  26. Tatake R. J., Amin K. M., Maniar H. S., Jambhekar N. A., Srikhande S. S., Gangal S. G. Monoclonal antibody against human squamous-cell-carcinoma-associated antigen. Int J Cancer. 1989 Nov 15;44(5):840–845. doi: 10.1002/ijc.2910440516. [DOI] [PubMed] [Google Scholar]
  27. Wahl R. L., Parker C. W., Philpott G. W. Improved radioimaging and tumor localization with monoclonal F(ab')2. J Nucl Med. 1983 Apr;24(4):316–325. [PubMed] [Google Scholar]
  28. Zenner H. P. Monoklonale Antikörper zur Erkennung von Larynxkarzinomzellen. Arch Otorhinolaryngol. 1981;233(2):161–172. doi: 10.1007/BF00453640. [DOI] [PubMed] [Google Scholar]

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

RESOURCES