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PMID: 2789951 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer.

British journal of cancer ·Vol. 60 ·No. 3 ·1989-09-00 ·Pages 406-12

Begent RH, Ledermann JA, Green AJ, Bagshawe KD, Riggs SJ, Searle F, Keep PA, Adam T, Dale RG, Glaser MG

Abstract

The distribution of iodine-131 (131I) labelled antibody to carcinoembryonic antigen (CEA) has been studied in 16 patients with colorectal cancer. Levels of tumour and normal tissue radioactivity were measured by serial gamma-camera imaging and counting of blood and urine. Maximum concentrations were found in tumour 8 h after administration and varied up to 9-fold in different patients. Higher levels were found on average in tumour than in any other tissue. Liver, lung and blood were the other tissues in which antibody was concentrated relative to the rest of the body. Antibody cleared from all these tissues over 1 week. Second antibody directed against the antitumour (first) antibody was given 24 h after first antibody in order to accelerate clearance from the blood. This increased the tumour to blood ratio but had little effect on other tissues. Cumulative radiation dose to tumour and normal tissue was estimated. In patients with the most efficient localisation the tumour to body ratio was 20:1 and tumour to blood ratio 5:1. This may be sufficient for effective therapy of cancer in patients selected for efficient antibody localisation. The data may be used to estimate the effect of different therapeutic strategies. For instance, in the time after second antibody administration the average tumour to blood ratio of radiation dose was 11:1, suggesting that two phase systems in which the therapeutic modality is given after a good tumour to normal tissue ratio is obtained may be effective for the majority of patients.

MeSH Terms
Antibodies, Neoplasm/analysis Carcinoembryonic Antigen/immunology Colonic Neoplasms/diagnostic imaging,radiotherapy Humans Iodine Radioisotopes/therapeutic use Radionuclide Imaging Radiotherapy Dosage Rectal Neoplasms/diagnostic imaging,radiotherapy
Chemicals
Antibodies, Neoplasm Carcinoembryonic Antigen Iodine Radioisotopes
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Begent R H
Department of Medical Oncology, Charing Cross and Westminster Medical School, London, UK.
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
References (26)
26 references, click to expand
  1. In vivo quantitation of lesion radioactivity using external counting methods.
    Med Phys. 1976 Jul-Aug;03(04):253-5 PMID: 958163
  2. Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: tumoricidal effects and distribution studies.
    Int J Cancer. 1985 Jun 15;35(6):715-20 PMID: 4008099
  3. Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody.
    Lancet. 1982 Oct 2;2(8301):739-42 PMID: 6125812
  4. Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.
    J Clin Oncol. 1987 Apr;5(4):562-73 PMID: 3549989
  5. A cytotoxic agent can be generated selectively at cancer sites.
    Br J Cancer. 1988 Dec;58(6):700-3 PMID: 3265633
  6. Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.
    Br J Cancer. 1988 Nov;58(5):654-7 PMID: 3265333
  7. Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.
    J Clin Oncol. 1985 Oct;3(10):1296-300 PMID: 4045523
  8. Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments.
    Cancer Treat Rep. 1984 Jan;68(1):317-28 PMID: 6607111
  9. Significance of circulatory clearance of tumour-localising IgG and F(ab')2 for potential therapy studied in a CEA-producing xenograft model.
    Tumour Biol. 1987;8(1):19-25 PMID: 3602844
  10. External imaging techniques for quantitation of distribution of I-131 F(ab')2 fragments of monoclonal antibody in humans.
    Med Phys. 1984 Nov-Dec;11(6):778-83 PMID: 6513886
  11. Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model.
    Cancer. 1988 May 1;61(9):1766-75 PMID: 2451555
  12. Iodine 131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group study.
    J Clin Oncol. 1985 Dec;3(12):1573-82 PMID: 2415692
  13. Antibody mediated delivery of toxic molecules to antigen bearing target cells.
    Immunol Rev. 1982;62:93-117 PMID: 6210622
  14. Tumor immunotherapy in the mouse with the use of 131I-labeled monoclonal antibodies.
    J Natl Cancer Inst. 1984 Mar;72(3):697-704 PMID: 6583453
  15. Therapeutic efficacy of antiglioma mesenchymal extracellular matrix 131I-radiolabeled murine monoclonal antibody in a human glioma xenograft model.
    Cancer Res. 1988 Feb 1;48(3):559-66 PMID: 2446747
  16. Anti-tumor effects of radiolabeled syngeneic monoclonal anti-melanoma antibodies.
    Gan. 1984 Aug;75(8):707-13 PMID: 6489678
  17. Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen.
    Cancer Res. 1981 Nov;41(11 Pt 1):4354-60 PMID: 7306964
  18. 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 PMID: 7189578
  19. Comparative tumor dose from 131I-labeled polyclonal anti-ferritin, anti-AFP, and anti-CEA in primary liver cancers.
    Cancer Drug Deliv. 1984 Fall;1(4):321-8 PMID: 6085756
  20. Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies.
    Cancer Res. 1986 Dec;46(12 Pt 1):6223-8 PMID: 3779642
  21. Radioimmunotherapy of the GW-39 human colonic tumor xenograft with 131I-labeled murine monoclonal antibody to carcinoembryonic antigen.
    Cancer Res. 1987 Nov 1;47(21):5672-7 PMID: 3664474
  22. The relation of radioiodine dosimetry to results and complications in the treatment of metastatic thyroid cancer.
    Am J Roentgenol Radium Ther Nucl Med. 1962 Jan;87:171-82 PMID: 13867399
  23. Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice.
    Cancer Res. 1986 Aug;46(8):3969-78 PMID: 3731067
  24. Dosimetry of 131I-labeled anti-ferritin in hepatoma: a model for radioimmunoglobulin dosimetry.
    Int J Radiat Oncol Biol Phys. 1981 Mar;7(3):323-33 PMID: 6268576
  25. Radioimmunotherapy of human colon carcinoma by 131I-labelled monoclonal anti-CEA antibodies in a nude mouse model.
    Int J Cancer. 1988 Jan 15;41(1):127-34 PMID: 3335416
  26. Experimental therapy of human breast tumors with 131I-labeled monoclonal antibodies prepared against the human milk fat globule.
    Cancer Res. 1988 Aug 15;48(16):4664-72 PMID: 3396015
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
1989-09-00
Pages
406-12
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2247181
Subset
IM
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