Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jan;77(1):301–311. doi: 10.1172/JCI112291

Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.

B Delaloye, A Bischof-Delaloye, F Buchegger, V von Fliedner, J P Grob, J C Volant, J Pettavel, J P Mach
PMCID: PMC423340  PMID: 3484753

Abstract

This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab')2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with 123I-labeled F(ab')2 (n = 14) or Fab (n = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintigraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.

Full text

PDF
301

Images in this article

Selected References

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

  1. Accolla R. S., Carrel S., Mach J. P. Monoclonal antibodies specific for carcinoembryonic antigen and produced by two hybrid cell lines. Proc Natl Acad Sci U S A. 1980 Jan;77(1):563–566. doi: 10.1073/pnas.77.1.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begent R. H., Keep P. A., Green A. J., Searle F., Bagshawe K. D., Jewkes R. F., Jones B. E., Barratt G. M., Ryman B. E. Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody. Lancet. 1982 Oct 2;2(8301):739–742. doi: 10.1016/s0140-6736(82)90923-0. [DOI] [PubMed] [Google Scholar]
  3. Berche C., Mach J. P., Lumbroso J. D., Langlais C., Aubry F., Buchegger F., Carrel S., Rougier P., Parmentier C., Tubiana M. Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen. Br Med J (Clin Res Ed) 1982 Nov 20;285(6353):1447–1451. doi: 10.1136/bmj.285.6353.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buchegger F., Haskell C. M., Schreyer M., Scazziga B. R., Randin S., Carrel S., Mach J. P. Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983 Aug 1;158(2):413–427. doi: 10.1084/jem.158.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buchegger F., Mettraux C., Accolla R. S., Carrel S., Mach J. P. Sandwich enzyme immunoassay using three monoclonal antibodies against different epitopes of carcinoembryonic antigen (CEA). Immunol Lett. 1982 Aug;5(2):85–91. doi: 10.1016/0165-2478(82)90038-4. [DOI] [PubMed] [Google Scholar]
  6. Buchegger F., Schreyer M., Carrel S., Mach J. P. Monoclonal antibodies identify a CEA crossreacting antigen of 95 kD (NCA-95) distinct in antigenicity and tissue distribution from the previously described NCA of 55 kD. Int J Cancer. 1984 May 15;33(5):643–649. doi: 10.1002/ijc.2910330515. [DOI] [PubMed] [Google Scholar]
  7. Chatal J. F., Saccavini J. C., Fumoleau P., Douillard J. Y., Curtet C., Kremer M., Le Mevel B., Koprowski H. Immunoscintigraphy of colon carcinoma. J Nucl Med. 1984 Mar;25(3):307–314. [PubMed] [Google Scholar]
  8. Dillman R. O., Beauregard J. C., Sobol R. E., Royston I., Bartholomew R. M., Hagan P. S., Halpern S. E. Lack of radioimmunodetection and complications associated with monoclonal anticarcinoembryonic antigen antibody cross-reactivity with an antigen on circulating cells. Cancer Res. 1984 May;44(5):2213–2218. [PubMed] [Google Scholar]
  9. Dykes P. W., Hine K. R., Bradwell A. R., Blackburn J. C., Reeder T. A., Drolc Z., Booth S. N. Localisation of tumour deposits by external scanning after injection of radiolabelled anti-carcinoembryonic antigen. Br Med J. 1980 Jan 26;280(6209):220–222. doi: 10.1136/bmj.280.6209.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Epenetos A. A., Britton K. E., Mather S., Shepherd J., Granowska M., Taylor-Papadimitriou J., Nimmon C. C., Durbin H., Hawkins L. R., Malpas J. S. Targeting of iodine-123-labelled tumour-associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumours. Lancet. 1982 Nov 6;2(8306):999–1005. doi: 10.1016/s0140-6736(82)90046-0. [DOI] [PubMed] [Google Scholar]
  11. Farrands P. A., Perkins A. C., Pimm M. V., Embleton M. J., Hardy J. D., Baldwin R. W., Hardcastle J. D. Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet. 1982 Aug 21;2(8295):397–400. doi: 10.1016/s0140-6736(82)90437-8. [DOI] [PubMed] [Google Scholar]
  12. GOLD P., FREEDMAN S. O. DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES. J Exp Med. 1965 Mar 1;121:439–462. doi: 10.1084/jem.121.3.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldenberg D. M., DeLand F., Kim E., Bennett S., Primus F. J., van Nagell J. R., Jr, Estes N., DeSimone P., Rayburn P. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med. 1978 Jun 22;298(25):1384–1386. doi: 10.1056/NEJM197806222982503. [DOI] [PubMed] [Google Scholar]
  14. Goldenberg D. M., Kim E. E., Bennett S. J., Nelson M. O., Deland F. H. Carcinoembryonic antigen radioimmunodetection in the evaluation of colorectal cancer and in the detection of occult neoplasms. Gastroenterology. 1983 Mar;84(3):524–532. [PubMed] [Google Scholar]
  15. Goldenberg D. M., Kim E. E., DeLand F. H., Bennett S., Primus F. J. Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Res. 1980 Aug;40(8 Pt 2):2984–2992. [PubMed] [Google Scholar]
  16. Goldenberg D. M., Preston D. F., Primus F. J., Hansen H. J. Photoscan localization of GW-39 tumors in hamsters using radiolabeled anticarcinoembryonic antigen immunoglobulin G. Cancer Res. 1974 Jan;34(1):1–9. [PubMed] [Google Scholar]
  17. Halpern S. E., Dillman R. O., Witztum K. F., Shega J. F., Hagan P. L., Burrows W. M., Dillman J. B., Clutter M. L., Sobol R. E., Frincke J. M. Radioimmunodetection of melanoma utilizing In-111 96.5 monoclonal antibody: a preliminary report. Radiology. 1985 May;155(2):493–499. doi: 10.1148/radiology.155.2.3983401. [DOI] [PubMed] [Google Scholar]
  18. Haskell C. M., Buchegger F., Schreyer M., Carrel S., Mach J. P. Monoclonal antibodies to carcinoembryonic antigen: ionic strength as a factor in the selection of antibodies for immunoscintigraphy. Cancer Res. 1983 Aug;43(8):3857–3864. [PubMed] [Google Scholar]
  19. Herlyn D. M., Steplewski Z., Herlyn M. F., Koprowski H. Inhibition of growth of colorectal carcinoma in nude mice by monoclonal antibody. Cancer Res. 1980 Mar;40(3):717–721. [PubMed] [Google Scholar]
  20. Keenan A. M., Colcher D., Larson S. M., Schlom J. Radioimmunoscintigraphy of human colon cancer xenografts in mice with radioiodinated monoclonal antibody B72.3. J Nucl Med. 1984 Nov;25(11):1197–1203. [PubMed] [Google Scholar]
  21. Khaw B. A., Strauss H. W., Cahill S. L., Soule H. R., Edgington T., Cooney J. Sequential imaging of indium-111-labeled monoclonal antibody in human mammary tumors hosted in nude mice. J Nucl Med. 1984 May;25(5):592–603. [PubMed] [Google Scholar]
  22. Khaw B. A., Strauss H. W., Carvalho A., Locke E., Gold H. K., Haber E. Technetium-99m labeling of antibodies to cardiac myosin Fab and to human fibrinogen. J Nucl Med. 1982 Nov;23(11):1011–1019. [PubMed] [Google Scholar]
  23. Koprowski H., Herlyn M., Steplewski Z., Sears H. F. Specific antigen in serum of patients with colon carcinoma. Science. 1981 Apr 3;212(4490):53–55. doi: 10.1126/science.6163212. [DOI] [PubMed] [Google Scholar]
  24. Larson S. M., Carrasquillo J. A., Krohn K. A., Brown J. P., McGuffin R. W., Ferens J. M., Graham M. M., Hill L. D., Beaumier P. L., Hellström K. E. Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy. J Clin Invest. 1983 Dec;72(6):2101–2114. doi: 10.1172/JCI111175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Larson S. M., Carrasquillo J. A., Krohn K. A., McGuffin R. W., Williams D. L., Hellström I., Lyster D. Diagnostic imaging of malignant melanoma with radiolabeled antitumor antibodies. JAMA. 1983 Feb 11;249(6):811–812. [PubMed] [Google Scholar]
  26. Larson S. M. Radiolabeled monoclonal anti-tumor antibodies in diagnosis and therapy. J Nucl Med. 1985 May;26(5):538–545. [PubMed] [Google Scholar]
  27. Mach J. P., Carrel S., Forni M., Ritschard J., Donath A., Alberto P. Tumor localization of radiolabeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation. N Engl J Med. 1980 Jul 3;303(1):5–10. doi: 10.1056/NEJM198007033030102. [DOI] [PubMed] [Google Scholar]
  28. Mach J. P., Carrel S., Merenda C., Sordat B., Cerottini J. C. In vivo localisation of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice. Nature. 1974 Apr 19;248(5450):704–706. doi: 10.1038/248704a0. [DOI] [PubMed] [Google Scholar]
  29. Mach J. P., Chatal J. F., Lumbroso J. D., Buchegger F., Forni M., Ritschard J., Berche C., Douillard J. Y., Carrel S., Herlyn M. Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma. Cancer Res. 1983 Nov;43(11):5593–5600. [PubMed] [Google Scholar]
  30. Mach J. P., Forni M., Ritschard J., Buchegger F., Carrel S., Widgren S., Donath A., Alberto P. Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas. Oncodev Biol Med. 1980 Aug;1(1):49–69. [PubMed] [Google Scholar]
  31. Moldofsky P. J., Powe J., Mulhern C. B., Jr, Hammond N., Sears H. F., Gatenby R. A., Steplewski Z., Koprowski H. Metastatic colon carcinoma detected with radiolabeled F(ab')2 monoclonal antibody fragments. Radiology. 1983 Nov;149(2):549–555. doi: 10.1148/radiology.149.2.6622704. [DOI] [PubMed] [Google Scholar]
  32. Murray J. L., Rosenblum M. G., Sobol R. E., Bartholomew R. M., Plager C. E., Haynie T. P., Jahns M. F., Glenn H. J., Lamki L., Benjamin R. S. Radioimmunoimaging in malignant melanoma with 111In-labeled monoclonal antibody 96.5. Cancer Res. 1985 May;45(5):2376–2381. [PubMed] [Google Scholar]
  33. Order S. E., Klein J. L., Ettinger D., Alderson P., Siegelman S., Leichner P. Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. Int J Radiat Oncol Biol Phys. 1980 Jun;6(6):703–710. doi: 10.1016/0360-3016(80)90226-6. [DOI] [PubMed] [Google Scholar]
  34. Ott R. J., Grey L. J., Zivanovic M. A., Flower M. A., Trott N. G., Moshakis V., Coombes R. C., Neville A. M., Ormerod M. G., Westwood J. H. The limitations of the dual radionuclide subtraction technique for the external detection of tumours by radioiodine-labelled antibodies. Br J Radiol. 1983 Feb;56(662):101–108. doi: 10.1259/0007-1285-56-662-101. [DOI] [PubMed] [Google Scholar]
  35. PRESSMAN D., DAY E. D., BLAU M. The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 1957 Oct;17(9):845–850. [PubMed] [Google Scholar]
  36. Rainsbury R. M., Ott R. J., Westwood J. H., Kalirai T. S., Coombes R. C., McCready V. R., Neville A. M., Gazet J. C. Location of metastatic breast carcinoma by a monoclonal antibody chelate labelled with indium-111. Lancet. 1983 Oct 22;2(8356):934–938. doi: 10.1016/s0140-6736(83)90452-x. [DOI] [PubMed] [Google Scholar]
  37. Taylor S. M., Bennett G. D., Abbott L. C., Finnell R. H. Seizure control following administration of anticonvulsant drugs in the quaking mouse. Eur J Pharmacol. 1985 Nov 26;118(1-2):163–170. doi: 10.1016/0014-2999(85)90675-2. [DOI] [PubMed] [Google Scholar]
  38. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES