Abstract
alpha-Particles such as those emitted by 211At may be advantageous for radioimmunotherapy since they are radiation of high linear energy transfer, depositing high energy over a short distance. Here we describe a strategy for labeling monoclonal antibodies and F(ab')2 fragments with 211At by means of the bifunctional reagent N-succinimidyl 3-(trimethylstannyl)benzoate. An intact antibody, 81C6, and the F(ab')2 fragment of Me1-14 (both reactive with human gliomas) were labeled with 211At in high yield and with a specific activity of up to 4 mCi/mg in a time frame compatible with the 7.2-hr half-life of 211At. Quantitative in vivo binding assays demonstrated that radioastatination was accomplished with maintenance of high specific binding and affinity. Comparison of the biodistribution of 211At-labeled Me1-14 F(ab')2 to that of a nonspecific antibody fragment labeled with 211At and 131I in athymic mice bearing D-54 MG human glioma xenografts demonstrated selective and specific targeting of 211At-labeled antibody in this human tumor model.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aaij C., Tschroots WRJM, Lindner L., Feltkamp T. E. The preparation of astatine labelled proteins. Int J Appl Radiat Isot. 1975 Jan;26(1):25–30. doi: 10.1016/0020-708x(75)90006-x. [DOI] [PubMed] [Google Scholar]
- Badger C. C., Krohn K. A., Peterson A. V., Shulman H., Bernstein I. D. Experimental radiotherapy of murine lymphoma with 131I-labeled anti-Thy 1.1 monoclonal antibody. Cancer Res. 1985 Apr;45(4):1536–1544. [PubMed] [Google Scholar]
- Barendsen G. W., Koot C. J., Van Kersen G. R., Bewley D. K., Field S. B., Parnell C. J. The effect of oxygen on impairment of the proliferative capacity of human cells in culture by ionizing radiations of different LET. Int J Radiat Biol Relat Stud Phys Chem Med. 1966;10(4):317–327. doi: 10.1080/09553006614550421. [DOI] [PubMed] [Google Scholar]
- Bateman W. J., Vaughan A. T., Brown G. Tumour localisation of 211At-labelled monoclonal antibody to a sub-cutaneous human heterograft in the nude mouse II. Int J Nucl Med Biol. 1983;10(4):241–244. doi: 10.1016/0047-0740(83)90087-6. [DOI] [PubMed] [Google Scholar]
- Bertsche U., Iliakis G., Kraft G. Inactivation of Ehrlich ascites tumor cells by heavy ions. Radiat Res. 1983 Jul;95(1):57–67. [PubMed] [Google Scholar]
- Bourdon M. A., Matthews T. J., Pizzo S. V., Bigner D. D. Immunochemical and biochemical characterization of a glioma-associated extracellular matrix glycoprotein. J Cell Biochem. 1985;28(3):183–195. doi: 10.1002/jcb.240280302. [DOI] [PubMed] [Google Scholar]
- Bourdon M. A., Wikstrand C. J., Furthmayr H., Matthews T. J., Bigner D. D. Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res. 1983 Jun;43(6):2796–2805. [PubMed] [Google Scholar]
- Buchegger F., Vacca A., Carrel S., Schreyer M., Mach J. P. 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):127–134. doi: 10.1002/ijc.2910410123. [DOI] [PubMed] [Google Scholar]
- Carrel S., Accolla R. S., Carmagnola A. L., Mach J. P. Common human melanoma-associated antigen(s) detected by monoclonal antibodies. Cancer Res. 1980 Jul;40(7):2523–2528. [PubMed] [Google Scholar]
- Colapinto E. V., Humphrey P. A., Zalutsky M. R., Groothuis D. R., Friedman H. S., de Tribolet N., Carrel S., Bigner D. D. Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts. Cancer Res. 1988 Oct 15;48(20):5701–5707. [PubMed] [Google Scholar]
- Friedman A. M., Zalutsky M. R., Wung W., Buckingham F., Scherr G. H., Wainer B., Hunter R. L., Appelman E. H., Rothberg R. M., Fitch F. W. Preparation of a biologically stable and immunogenically competent astatinated protein. Int J Nucl Med Biol. 1977 Dec;4(3-4):219–224. doi: 10.1016/0047-0740(77)90146-2. [DOI] [PubMed] [Google Scholar]
- Friedman H. S., Bigner S. H., McComb R. D., Schold S. C., Jr, Pasternak J. F., Groothuis D. R., Bigner D. D. A model for human medulloblastoma. Growth, morphology, and chromosomal analysis in vitro and in athymic mice. J Neuropathol Exp Neurol. 1983 Sep;42(5):485–503. doi: 10.1097/00005072-198309000-00001. [DOI] [PubMed] [Google Scholar]
- Garg P. K., Archer G. E., Jr, Bigner D. D., Zalutsky M. R. Synthesis of radioiodinated N-succinimidyl iodobenzoate: optimization for use in antibody labelling. Int J Rad Appl Instrum A. 1989;40(6):485–490. doi: 10.1016/0883-2889(89)90131-7. [DOI] [PubMed] [Google Scholar]
- Harrison A., Royle L. Efficacy of astatine-211-labeled monoclonal antibody in treatment of murine T-cell lymphoma. NCI Monogr. 1987;(3):157–158. [PubMed] [Google Scholar]
- Harrison A., Royle L. Preparation of a 211At-IgG conjugate which is stable in vivo. Int J Appl Radiat Isot. 1984 Nov;35(11):1005–1008. doi: 10.1016/0020-708x(84)90001-2. [DOI] [PubMed] [Google Scholar]
- Humm J. L. A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy. Int J Radiat Oncol Biol Phys. 1987 Nov;13(11):1767–1773. doi: 10.1016/0360-3016(87)90176-3. [DOI] [PubMed] [Google Scholar]
- Kassis A. I., Harris C. R., Adelstein S. J., Ruth T. J., Lambrecht R., Wolf A. P. The in vitro radiobiology of astatine-211 decay. Radiat Res. 1986 Jan;105(1):27–36. [PubMed] [Google Scholar]
- Kozak R. W., Atcher R. W., Gansow O. A., Friedman A. M., Hines J. J., Waldmann T. A. Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy. Proc Natl Acad Sci U S A. 1986 Jan;83(2):474–478. doi: 10.1073/pnas.83.2.474. [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]
- Lee Y. S., Bullard D. E., Zalutsky M. R., Coleman R. E., Wikstrand C. J., Friedman H. S., Colapinto E. V., Bigner D. D. 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):559–566. [PubMed] [Google Scholar]
- Lee Y., Bullard D. E., Humphrey P. A., Colapinto E. V., Friedman H. S., Zalutsky M. R., Coleman R. E., Bigner D. D. Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6. Cancer Res. 1988 May 15;48(10):2904–2910. [PubMed] [Google Scholar]
- Macklis R. M., Kinsey B. M., Kassis A. I., Ferrara J. L., Atcher R. W., Hines J. J., Coleman C. N., Adelstein S. J., Burakoff S. J. Radioimmunotherapy with alpha-particle-emitting immunoconjugates. Science. 1988 May 20;240(4855):1024–1026. doi: 10.1126/science.2897133. [DOI] [PubMed] [Google Scholar]
- McPherson G. A. A practical computer-based approach to the analysis of radioligand binding experiments. Comput Programs Biomed. 1983 Aug-Oct;17(1-2):107–113. doi: 10.1016/0010-468x(83)90031-4. [DOI] [PubMed] [Google Scholar]
- Moshakis V., McIlhinney R. A., Raghavan D., Neville A. M. Localization of human tumour xenografts after i.v. administration of radiolabeled monoclonal antibodies. Br J Cancer. 1981 Jul;44(1):91–99. doi: 10.1038/bjc.1981.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ritter M. A., Cleaver J. E., Tobias C. A. High-LET radiations induce a large proportion of non-rejoining DNA breaks. Nature. 1977 Apr 14;266(5603):653–655. doi: 10.1038/266653a0. [DOI] [PubMed] [Google Scholar]
- Sharkey R. M., Pykett M. J., Siegel J. A., Alger E. A., Primus F. J., Goldenberg D. M. 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):5672–5677. [PubMed] [Google Scholar]
- Singer K. H., Scearce R. M., Tuck D. T., Whichard L. P., Denning S. M., Haynes B. F. Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages. J Invest Dermatol. 1989 Feb;92(2):166–170. doi: 10.1111/1523-1747.ep12276685. [DOI] [PubMed] [Google Scholar]
- Vaughan A. T., Bateman W. J., Brown G., Cowan J. The specific inhibition of cellular clonogenic proliferation using 211At labelled lectins and antibodies--I. Int J Nucl Med Biol. 1982;9(3):167–171. doi: 10.1016/0047-0740(82)90091-2. [DOI] [PubMed] [Google Scholar]
- Vaughan A. T., Bateman W. J., Fisher D. R. The in vivo fate of a 211At labelled monoclonal antibody with known specificity in a murine system. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1943–1946. doi: 10.1016/0360-3016(82)90453-9. [DOI] [PubMed] [Google Scholar]
- Vaughan A. T., Fremlin J. H. The preparation of astatine labelled proteins using an electrophilic reaction. Int J Nucl Med Biol. 1978;5(6):229–230. doi: 10.1016/0047-0740(78)90145-6. [DOI] [PubMed] [Google Scholar]
- Ward B. G., Mather S. J., Hawkins L. R., Crowther M. E., Shepherd J. H., Granowska M., Britton K. E., Slevin M. L. Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration. Cancer Res. 1987 Sep 1;47(17):4719–4723. [PubMed] [Google Scholar]
- Zalutsky M. R., Narula A. S. A method for the radiohalogenation of proteins resulting in decreased thyroid uptake of radioiodine. Int J Rad Appl Instrum A. 1987;38(12):1051–1055. doi: 10.1016/0883-2889(87)90069-4. [DOI] [PubMed] [Google Scholar]
- Zalutsky M. R., Narula A. S. Astatination of proteins using an N-succinimidyl tri-n-butylstannyl benzoate intermediate. Int J Rad Appl Instrum A. 1988;39(3):227–232. doi: 10.1016/0883-2889(88)90176-1. [DOI] [PubMed] [Google Scholar]