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. 1992 Jun;65(6):825–831. doi: 10.1038/bjc.1992.176

Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy.

G M Boxer 1, R H Begent 1, A M Kelly 1, P J Southall 1, S B Blair 1, N A Theodorou 1, P M Dawson 1, J A Ledermann 1
PMCID: PMC1977772  PMID: 1616854

Abstract

Tumour localisation of anti-tumour antibodies varies greatly between patients. Factors which may be responsible for this have been investigated in 56 patients with colorectal carcinoma with a view to improving radioimmunotherapy. Thirty-seven to seventy-four MBq of 125-I labelled mouse monoclonal antibody to CEA, was given intravenously and tumour resected 70-480 h later. Percentage injected activity kg-1 (% inj.act kg-1) in tumour, was inversely correlated with the time interval between injection and operation (P = 0.004). To assess the influence of other parameters on localisation, patients were divided into two time groups according to time interval between injection and operation, 70-120 h (n = 33) and 144-480 h (n = 23). In neither group was there a significant correlation of % inj.act kg-1 with time. The % inj.act kg-1 in tumour showed a significant correlation with that in the blood for both groups (P = 0.005 and P = 0.01). There was no significant correlation for either time group between % inj.act kg-1 in tumour and serum CEA values, the per cent of tumour cells positive for CEA and vascularity. Tumour to blood ratios varied considerably (range 0.3-28.5:1) suggesting that factors other than time and persistence of activity in the blood contribute to efficient targeting. Tumour to blood ratios were inversely correlated with % inj.act kg-1 in blood for the 70-120 h group (P = 0.007), and were positively correlated with % inj.act kg-1 in tumour (P = 0.012). Autoradiography showed that antibody localised predominantly on tumour cells but was distributed heterogeneously, was not solely related to the expression of antigen and in some cases accumulated in necrotic more than viable areas of tumour. Penetration of antibody into malignant acinar structures was poor and CEA-positive cells closer to the blood supply were targeted to a greater extent than distant cells. Preoperative administration of radiolabelled antibody to CEA may be helpful in selecting patients with favourable localisation for radioimmunotherapy.

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Selected References

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

  1. Begent R. H., Ledermann J. A., Green A. J., Bagshawe K. D., Riggs S. J., Searle F., Keep P. A., Adam T., Dale R. G., Glaser M. G. Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer. Br J Cancer. 1989 Sep;60(3):406–412. doi: 10.1038/bjc.1989.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blair S. D., Theodorou N. A., Begent R. H., Dawson P. M., Salmon M., Riggs S., Kelly A., Boxer G., Southall P., Gregory P. Comparison of anti-fetal colonic microvillus and anti-CEA antibodies in peroperative radioimmunolocalisation of colorectal cancer. Br J Cancer. 1990 Jun;61(6):891–894. doi: 10.1038/bjc.1990.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Green A. J., Dewhurst S. E., Begent R. H., Bagshawe K. D., Riggs S. J. Accurate quantification of 131I distribution by gamma camera imaging. Eur J Nucl Med. 1990;16(4-6):361–365. doi: 10.1007/BF00842793. [DOI] [PubMed] [Google Scholar]
  5. Griffith M. H., Yorke E. D., Wessels B. W., DeNardo G. L., Neacy W. P. Direct dose confirmation of quantitative autoradiography with micro-TLD measurements for radioimmunotherapy. J Nucl Med. 1988 Nov;29(11):1795–1809. [PubMed] [Google Scholar]
  6. Harwood P. J., Britton D. W., Southall P. J., Boxer G. M., Rawlins G., Rogers G. T. Mapping epitope characteristics on carcinoembryonic antigen. Br J Cancer. 1986 Jul;54(1):75–82. doi: 10.1038/bjc.1986.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Humm J. L., Cobb L. M. Nonuniformity of tumor dose in radioimmunotherapy. J Nucl Med. 1990 Jan;31(1):75–83. [PubMed] [Google Scholar]
  8. Jain R. K., Baxter L. T. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res. 1988 Dec 15;48(24 Pt 1):7022–7032. [PubMed] [Google Scholar]
  9. Martin E. W., Jr, Mojzisik C. M., Hinkle G. H., Jr, Sampsel J., Siddiqi M. A., Tuttle S. E., Sickle-Santanello B., Colcher D., Thurston M. O., Bell J. G. Radioimmunoguided surgery using monoclonal antibody. Am J Surg. 1988 Nov;156(5):386–392. doi: 10.1016/s0002-9610(88)80193-4. [DOI] [PubMed] [Google Scholar]
  10. Martin K. W., Halpern S. E. Carcinoembryonic antigen production, secretion, and kinetics in BALB/c mice and a nude mouse-human tumor model. Cancer Res. 1984 Dec;44(12 Pt 1):5475–5481. [PubMed] [Google Scholar]
  11. Pedley R. B., Boden J. A., Boden R. W., Green A., Boxer G. M., Bagshawe K. D. The effect of serum CEA on the distribution and clearance of anti-CEA antibody in a pancreatic tumour xenograft model. Br J Cancer. 1989 Oct;60(4):549–554. doi: 10.1038/bjc.1989.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pedley R. B., Boden J., Keep P. A., Harwood P. J., Green A. J., Rogers G. T. Relationship between tumour size and uptake of radiolabelled anti-CEA in a colon tumour xenograft. Eur J Nucl Med. 1987;13(4):197–202. doi: 10.1007/BF00256491. [DOI] [PubMed] [Google Scholar]
  13. Pedley R. B., Boxer G. M., Boden J. A., Southall P. J., Begent R. H., Bagshawe K. D., Humm J., Searle F. Preliminary observations on the microdistribution of labelled antibodies in human colonic adenocarcinoma xenografts: relevance to microdosimetry. Br J Cancer. 1990 Feb;61(2):218–220. doi: 10.1038/bjc.1990.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sampsel J. W., Hinkle G., Nieroda C., Ignaszewski J., Thurston M., Martin E. W. Gamma-detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX-1 colon xenografts. J Surg Oncol. 1990 Dec;45(4):242–249. doi: 10.1002/jso.2930450407. [DOI] [PubMed] [Google Scholar]
  15. Sankey E. A., More L., Dhillon A. P. QBEnd/10: a new immunostain for the routine diagnosis of Kaposi's sarcoma. J Pathol. 1990 Jul;161(3):267–271. doi: 10.1002/path.1711610315. [DOI] [PubMed] [Google Scholar]
  16. Southall P. J., Boxer G. M., Bagshawe K. D., Hole N., Bromley M., Stern P. L. Immunohistological distribution of 5T4 antigen in normal and malignant tissues. Br J Cancer. 1990 Jan;61(1):89–95. doi: 10.1038/bjc.1990.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Steis R. G., Carrasquillo J. A., McCabe R., Bookman M. A., Reynolds J. C., Larson S. M., Smith J. W., 2nd, Clark J. W., Dailey V., Del Vecchio S. Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma. J Clin Oncol. 1990 Mar;8(3):476–490. doi: 10.1200/JCO.1990.8.3.476. [DOI] [PubMed] [Google Scholar]
  18. Sutherland R., Buchegger F., Schreyer M., Vacca A., Mach J. P. Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids. Cancer Res. 1987 Mar 15;47(6):1627–1633. [PubMed] [Google Scholar]
  19. Tuttle S. E., Jewell S. D., Mojzisik C. M., Hinkle G. H., Colcher D., Schlom J., Martin E. W. Intraoperative radioimmunolocalization of colorectal carcinoma with a hand-held gamma probe and MAb B72.3: comparison of in vivo gamma probe counts with in vitro MAb radiolocalization. Int J Cancer. 1988 Sep 15;42(3):352–358. doi: 10.1002/ijc.2910420308. [DOI] [PubMed] [Google Scholar]

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