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. 1999 May;80(5-6):922–926. doi: 10.1038/sj.bjc.6690443

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome

G Boxer 1, S Stuart-Smith 1, A Flynn 1, A Green 1, R Begent 1
PMCID: PMC2362277  PMID: 10360677

Abstract

Proteins control cell function and measurement of their concentration is crucial for understanding their roles in health and disease. However, current methods for their detection in tissue sections are not quantitative. Radioimmunoluminography (RILG) is a system for direct measurement of quantity and distribution of protein in histological sections. Histological carcinomas were reacted with antigen-saturating concentrations of 125I-antibody to carcinoembryonic antigen (CEA). Antibody distribution and concentration was mapped by phosphor imaging. Radioactivity in each pixel of the digital image was proportional to antigen concentration, calculated from a standard line generated from a nitrocellulose CEA dot-blot assay. RILG gave a linear correlation with standards of known CEA concentration (r = 0.999). Six tumour xenografts with differing CEA concentrations by radioimmunoassay (RIA) were studied by RILG and immunohistochemistry (IHC). RILG gave a linear correlation with CEA by RIA (r = 0.994) but IHC failed to do so (r = 0.42). CEA levels measured by RILG, in cryostat (n = 15) and paraffin (n = 19) sections from colorectal cancer patients showed a range of CEA concentration (38.9–594 ng g−1 and 22.5–212.5 ng g−1 respectively). Tumour CEA concentration by RILG was significantly correlated with dose of antibody (% injected radioactivity kg−1) localized in tumour (P = 0.04 and P < 0.02 respectively), in patients receiving radioimmunoguided surgery. Clinical relevance of RILG is illustrated by identifying patients with high tumour CEA, most likely to benefit from antibody targeted therapy. Knowledge of the pathophysiology of many diseases may be enhanced by quantitative estimation of antigen concentration related to tissue morphology. © 1999 Cancer Research Campaign

Keywords: quantification, immunohistochemistry, radioluminography, phosphor image, colorectal cancer, targeting

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Selected References

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  1. 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]
  2. Boxer G. M., Begent R. H., Kelly A. M., Southall P. J., Blair S. B., Theodorou N. A., Dawson P. M., Ledermann J. A. Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy. Br J Cancer. 1992 Jun;65(6):825–831. doi: 10.1038/bjc.1992.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chung J. K., Jang J. J., Lee D. S., Lee M. C., Koh C. S. Tumor concentration and distribution of carcinoembryonic antigen measured by in vitro quantitative autoradiography. J Nucl Med. 1994 Sep;35(9):1499–1505. [PubMed] [Google Scholar]
  4. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Hitchins R. N., Begent R. H., Green A. J., Searle F., van Heyningen V., Bagshawe K. D. Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours. Nuklearmedizin. 1989 Feb;28(1):29–33. [PubMed] [Google Scholar]
  7. Jain R. K. Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J Natl Cancer Inst. 1989 Apr 19;81(8):570–576. doi: 10.1093/jnci/81.8.570. [DOI] [PubMed] [Google Scholar]
  8. Lane D. M., Eagle K. F., Begent R. H., Hope-Stone L. D., Green A. J., Casey J. L., Keep P. A., Kelly A. M., Ledermann J. A., Glaser M. G. Radioimmunotherapy of metastatic colorectal tumours with iodine-131-labelled antibody to carcinoembryonic antigen: phase I/II study with comparative biodistribution of intact and F(ab')2 antibodies. Br J Cancer. 1994 Sep;70(3):521–525. doi: 10.1038/bjc.1994.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marshall D., Pedley R. B., Melton R. G., Boden J. A., Boden R., Begent R. H. Galactosylated streptavidin for improved clearance of biotinylated intact and F(ab')2 fragments of an anti-tumour antibody. Br J Cancer. 1995 Jan;71(1):18–24. doi: 10.1038/bjc.1995.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Okuyama M., Hatori Y., Shigematsu A. Autoradioluminography, a novel quantitative method of TLC-autoradiography. Biol Pharm Bull. 1994 May;17(5):559–563. doi: 10.1248/bpb.17.559. [DOI] [PubMed] [Google Scholar]
  11. Pedley R. B., Boden J. A., Boden R., Boxer G. M., Flynn A. A., Keep P. A., Begent R. H. Ablation of colorectal xenografts with combined radioimmunotherapy and tumor blood flow-modifying agents. Cancer Res. 1996 Jul 15;56(14):3293–3300. [PubMed] [Google Scholar]
  12. Poznansky M. J., Juliano R. L. Biological approaches to the controlled delivery of drugs: a critical review. Pharmacol Rev. 1984 Dec;36(4):277–336. [PubMed] [Google Scholar]
  13. Shockley T. R., Lin K., Nagy J. A., Tompkins R. G., Dvorak H. F., Yarmush M. L. Penetration of tumor tissue by antibodies and other immunoproteins. Ann N Y Acad Sci. 1991;618:367–382. doi: 10.1111/j.1749-6632.1991.tb27257.x. [DOI] [PubMed] [Google Scholar]
  14. 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]

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