Summary
A monoclonal anti-CEA antibody (1H12) has been examined for the effect of dosage on tumour localisation in immunodeprived mice xenografted with human colon carcinoma. Increased doses produced a linear rise in the absolute concentration found in the tumour but this was found to depend on tumour size, with the smaller tumours (mean weight 44 mg) accumulating significantly more antibody compared to larger tumours (mean weight 146 mg). With the smallest tumour (18 mg), in which saturation was achieved, a 500 μg dose produced a concentration in tumour of 60 μg/g. In the larger tumours a dose of 256 μg produced a mean concentration of 5.2 μg/g. Prolonged retention of 1H12 by tumour up to 8 days, observed at doses of 4, 128 and 256 μg, indicated that the dynamics of localisation is unaffected by dosage.
Increased doses of 125I-1H12 caused an increase in the levels of radioactivity associated with all normal tissues studied. Thus at 8 days after injection an increase from 4 to 128 μg produced 50% and 42% declines in the tumour to blood and liver ratios, respectively. Cumulative localisation of 1H12 in tumour, from 4 h to 8 days, relative to normal tissue clearance was diminished on increasing dosage. This study shows that attempted therapy with escalated amounts of intact antibody is likely to be limited by a protracted excretory process and measures aimed at accelerating circulatory clearance are necessary.
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References
Barratt GM, Ryman BE, Begent RHJ, Keep PA, Searle F, Boden J, Bagshawe KD (1983) Improved radioimmunodetection of tumour using liposome-entrapped antibody. Biochim Biophys Acta 762:154
Begent RHJ (1985) Recent advances in tumour imaging: Use of radiolabelled anti-tumour antibodies. Biochim Biophys Acta 780:151
Carrasquillo JA, Krohn KA, Beaumier P, McGuffin RW, Brown JP, Hellstrom KE, Hellstrom I, Larson SM (1984) Diagnosis of and therapy for solid tumours with radiolabelled antibodies and immune fragments. Cancer Treat Rep 68:317
Goldenberg DM, Gaffar SA, Bennett SJ, Beach JL (1981) Experimental immunoradiotherapy of xenografted human colonic tumour (GW-39) producing carcinoembryonic antigen. Cancer Res 41:4354
Hagan PL, Halpern SE, Dillman RO, Shawler DL, Johnson DE, Chen A, Krishnan L, Frincke J, Bartholomew RM, David GS, Carlo D (1986) Tumour size: Effect on monoclonal antibody uptake in tumour models. J Nucl Med 27:422
Harwood PJ, Britton DW, Southall PJ, Boxer GM, Rawlins G, Rogers GT (1986) Mapping epitope characteristics on carcinoembryonic antigen. Br J Cancer 54:75
Hedin A, Wahren B, Hammarstrom S (1982) Tumour localisation of CEA-containing human tumours in nude mice by means of monoclonal anti-CEA antibodies. Int J Cancer 30:547
Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of pre-defined specificity. Nature 256:495
Leichner PK, Klein JL, Fishman EK, Seligman SS, Ettinger DS, Order SE (1984) Comparative tumour dose from 131I-labelled polyclonal anti-ferritin, anti-AFP, anti-CEA in primary liver cancers. Cancer Drug Delivery 1:321
Mach J-P, Forni M, Ritschard J, Buchegger F, Carrel S, Widgren S, Donath A, Alberto P (1980) Use and limitations of radiolabelled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas. Oncodev Biol Med 1:49
Mach J-P, Buchegger F, Forni M, Ritschard J, Berche C, Lumbroso J-D, Schreyer M, Giradet C, Accolla RS, Carrel S (1981) Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintography. Immunol Today 2:239
Moshakis V, McIlhinney RAJ, Raghavan D, Neville AM (1981) Localisation of human tumour xenografts after i.v. administration of radiolabelled monoclonal antibodies. Br J Cancer 44:91
Pimm MV, Baldwin RW (1984) Quantitative evaluation of the localisation of a monoclonal antibody (791T/36) in human osteogenic sarcoma xenografts. Eur J Cancer Clin Oncol 20:515
Pimm MV, Armitage NC, Perkins AC, Smith W, Baldwin RW (1985) Localisation of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts. Cancer Immunol Immunother 19:8
Pressman D (1957) Radiolabelled antibodies. Ann NY Acad Sci 69:644
Primus FJ, Wang RH, Goldenberg DM, Hansen HJ (1973) Localisation of human GW-39 tumours in hamsters by radio-labelled heterospecific antibody to carcinoembryonic antigen. Cancer Res 33:2477
Rogers GT (1986) Limitations associated with the use or radiolabelled antibodies against CEA for potential tumour localisation and therapy. Eur J Cancer Clin Oncol (in press)
Rogers GT, Harwood PJ, Pedley RB, Boden J, Rawlins G, Bagshawe KD (1985) Dynamics of monoclonal antibody distribution and prolonged tumour localisation in nude mice bearing a human CEA-producing colon carcinoma xenograft. Tumour Biol 6:453
Rogers GT, Harwood PJ, Pedley RB, Boden J, Bagshawe KD (1986) Dose-dependent localisation and potential for therapy of F(ab')2 fragments against CEA studied in a human tumour xenograft model. Br J Cancer (in press)
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Rogers, G.T., Pedley, R.B., Boden, J. et al. Effect of dose escalation of a monoclonal anti-CEA IgG on tumour localisation and tissue distribution in nude mice xenografted with human colon carcinoma. Cancer Immunol Immunother 23, 107–112 (1986). https://doi.org/10.1007/BF00199815
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DOI: https://doi.org/10.1007/BF00199815