Abstract
A pilot study was undertaken to determine the feasibility of infusing 131I labelled monoclonal antibodies (MoAbs) into either the cavity remaining after resection of malignant glioma or into glioma cysts. Of the seven patients recruited into the study, two had cystic lesions and five resection cavities. Six of the seven were treated after relapse from primary therapy. All patients apart from one, were given a single injection of 131I conjugated to a MoAb (ERIC-1) recognising the human neural cell adhesion molecule (NCAM). One patient received a further injection of 131I-MoAb after regrowth of their disease. Pharmacokinetic studies revealed that the MoAb remained predominantly in the tumour cavity with little leakage into the systemic compartment. This resulted in a high calculated dose of radiation being delivered to the tumour cells either lining or within close proximity to the cavity/cyst wall. In such a small study, it is not possible to determine accurately response rates, but individual patient responses were observed. This, along with the low toxicity noted, demonstrates the feasibility of using 131I-MoAbs in this way. With 131I, radiation dose is deposited in tissue to a depth of 1 mm from the source. The possibility of applying isotopes such as 90Yttrium which will irradiate tumour/tissue to a greater depth (6 mm) is discussed in context with the biology of glioma infiltration into normal brain parenchyma.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bourne S. P., Patel K., Walsh F., Popham C. J., Coakham H. B., Kemshead J. T. A monoclonal antibody (ERIC-1), raised against retinoblastoma, that recognizes the neural cell adhesion molecule (NCAM) expressed on brain and tumours arising from the neuroectoderm. J Neurooncol. 1991 Apr;10(2):111–119. doi: 10.1007/BF00146871. [DOI] [PubMed] [Google Scholar]
- 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]
- Halperin E. C., Burger P. C., Bullard D. E. The fallacy of the localized supratentorial malignant glioma. Int J Radiat Oncol Biol Phys. 1988 Aug;15(2):505–509. doi: 10.1016/s0360-3016(98)90036-0. [DOI] [PubMed] [Google Scholar]
- Jain R. K. Haemodynamic and transport barriers to the treatment of solid tumours. Int J Radiat Biol. 1991 Jul-Aug;60(1-2):85–100. doi: 10.1080/09553009114551621. [DOI] [PubMed] [Google Scholar]
- Jain R. K. Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev. 1990 Nov;9(3):253–266. doi: 10.1007/BF00046364. [DOI] [PubMed] [Google Scholar]
- Kemshead J. T., Jones D. H., Goldman A., Richardson R. B., Coakham H. B. Is there a role for radioimmunolocalization in diagnosis of intracranial malignancies?: discussion paper. J R Soc Med. 1984 Oct;77(10):847–854. doi: 10.1177/014107688407701010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lashford L. S., Davies A. G., Richardson R. B., Bourne S. P., Bullimore J. A., Eckert H., Kemshead J. T., Coakham H. B. A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. Cancer. 1988 Mar 1;61(5):857–868. doi: 10.1002/1097-0142(19880301)61:5<857::aid-cncr2820610502>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Lindmo T., Boven E., Cuttitta F., Fedorko J., Bunn P. A., Jr Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1984 Aug 3;72(1):77–89. doi: 10.1016/0022-1759(84)90435-6. [DOI] [PubMed] [Google Scholar]
- Moi M. K., DeNardo S. J., Meares C. F. Stable bifunctional chelates of metals used in radiotherapy. Cancer Res. 1990 Feb 1;50(3 Suppl):789s–793s. [PubMed] [Google Scholar]
- Moseley R. P., Davies A. G., Richardson R. B., Zalutsky M., Carrell S., Fabre J., Slack N., Bullimore J., Pizer B., Papanastassiou V. Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis. Br J Cancer. 1990 Oct;62(4):637–642. doi: 10.1038/bjc.1990.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pizer B., Papanastassiou V., Hancock J., Cassano W., Coakham H., Kemshead J. A pilot study of monoclonal antibody targeted radiotherapy in the treatment of central nervous system leukaemia in children. Br J Haematol. 1991 Apr;77(4):466–472. doi: 10.1111/j.1365-2141.1991.tb08611.x. [DOI] [PubMed] [Google Scholar]
- Sands H., Jones P. L., Shah S. A., Palme D., Vessella R. L., Gallagher B. M. Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell xenografts. Cancer Res. 1988 Jan 1;48(1):188–193. [PubMed] [Google Scholar]
- Stewart J. S., Hird V., Snook D., Dhokia B., Sivolapenko G., Hooker G., Papadimitriou J. T., Rowlinson G., Sullivan M., Lambert H. E. Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer. J Clin Oncol. 1990 Dec;8(12):1941–1950. doi: 10.1200/JCO.1990.8.12.1941. [DOI] [PubMed] [Google Scholar]
- Vriesendorp H. M., Herpst J. M., Germack M. A., Klein J. L., Leichner P. K., Loudenslager D. M., Order S. E. Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01. J Clin Oncol. 1991 Jun;9(6):918–928. doi: 10.1200/JCO.1991.9.6.918. [DOI] [PubMed] [Google Scholar]

