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Diverse characteristics of111In labelled anti-CEA monoclonal antibodies for tumour immunoscintigraphy: Radiolabelling, biodistribution and imaging studies in mice with human tumour xenografts

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Abstract

Three monoclonal anti-CEA antibodies, designated 161, 198 (both IgG1) and 228 (IgG2a) have been labelled with111In via DTPA chelation and assessed for localization in human gastro-intestinal carcinomas as xenografts in athymic nude mice. Following reaction of the antibodies with DTPA anhydride, efficiency of chelation of111In varied between the antibodies with mean values of 30%, 52% and 62% with 161, 198 and 228 respectively. Gel filtration chromatography with all three labelled antibodies showed radiolabel predominantly coincident with IgG with little radioactivity in either high molecular weight form or as free111In. However, the efficiency of binding of radiolabelled antibodies to CEA producing tumour cells varied, with maxima of 42%, 65% and 20% for 161, 198 and 228. In vivo, in mice,111In was excreted at virtually identical rates (half times approx. 12 days) with all three prepartions and this was similar to the clearance of indium injected as111In-indium chloride, but111In-DTPA was rapidly eliminated (half time approximately 5 h). After injection inton mice with CEA producing xenografts of colon carcinoma HT29 and LS174T and gastric carcinoma MKN 45, circulating radiolabel was still predominantly in the form of labelled antibody with little or no detectable immune complexes or111In labelled transferrin. Tumour localization of all three antibodies was visualized by gamma camera imaging with target: non target ratios of up to 5:1. Dissection of mice with MKN45 gastric carcinoma xenograft showed 16%, 19.5% and 13% of the injected dose of111In from 161, 198 and 228 antibodies in each g of tumour tissue. Tumour to liver ratios were 3.8:1, 3.4:1 and 3.3:1. Similar studies in mice with xenografts of a human osteosarcoma, virtually devoid of CEA, showed no tumour localization with any of the antibodies (tumour: liver ratios <0.8:1).

These studies illustrate the diverse nature of anti-CEA antibodies as bases for radiopharmaceutical preparations, and emphasise that in vitro criteria alone may not reflect in vivo tumour localization capacity.

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Correspondence to Malcolm V. Pimm.

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Pimm, M.V., Perkins, A.C. & Baldwin, R.W. Diverse characteristics of111In labelled anti-CEA monoclonal antibodies for tumour immunoscintigraphy: Radiolabelling, biodistribution and imaging studies in mice with human tumour xenografts. Eur J Nucl Med 12, 515–521 (1987). https://doi.org/10.1007/BF00620477

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Key words

  • Monoclonal antibodies
  • Anti CEA
  • 111In labelling