Chemistry of inorganic compounds – Treating mixture to obtain metal containing compound – Radioactive metal
Patent
1999-01-28
2000-10-03
Mai, Ngoclan
Chemistry of inorganic compounds
Treating mixture to obtain metal containing compound
Radioactive metal
423249, 250432PD, 424 111, 210682, C01G 2900, G21G 404
Patent
active
061269093
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
This invention relates to a process and apparatus for the production of bismuth-212 (Bi-212) and a use for Bi-212. More particularly, the invention relates to a process and apparatus for the production of substantially radio-impurity-free bismuth-212 from a starting material containing lead-212 and a therapeutic use for the bismuth-212.
2. Background of the Invention
Ovarian carcinoma has the highest mortality rate of any gynecologic cancer. This is due, in part, to the spread of the disease outside of the pelvis by the time the disease is diagnosed. Cytoreductive surgery and therapy have improved the overall survival rate of patients with ovarian carcinoma. However, relapses have been observed even after apparent complete remission.
Initial treatment of patients whose cancers have reached stages III and IV with multiple chemotherapy agents yields positive responses in about 90 percent of the patients. However, after four years, only about 30 percent of the patients are expected to survive. Thigpen et al., Semin. Oncol., 16(Suppl. 6):58 (1989). Current treatment strategies following relapse include intraperitoneal chemotherapy and abdominopelvic external beam therapy. These treatments have usually been found to be ineffective.
Radiation therapy, such as X-ray therapy, has been observed to be the most effective treatment for microscopic disease. Microscopic disease refers to the layers of cells remaining after removal of a tumor, cells of a tumor that are beginning to form and the first few cell layers of tumor growth and formation. The use of radiation therapy is limited to the radio tolerance of normal cells and by technical problems encountered in delivering tumoricidal doses.
In addition, it is believed that when the tumor does not respond to conventional radiation therapy this may be due, in part, to the quality of radiation that is used. For example, X-ray therapy is low-LET (linear energy transfer), is sparsely ionizing and its effectiveness is dependent on cellular oxygen.
Radionuclide therapy using chromic phosphate (P-32), which is a low-LET beta-emitter, has exhibited some level of success. A five-year survival rate of 81 percent for the treatment of microscopic disease has been reported for patients with stage I and stage II disease. Young et al., N. Eng. J. Med., 322:1021 (1990). Nevertheless, similar to X-ray therapy, P-32 is low-LET, is sparsely ionizing and its effectiveness is dependent on cellular oxygen.
Alpha-emitting radionuclides have also been found to be effective in the treatment and eradication of microscopic carcinoma in animal models. This is believed to be a result of the densely ionizing radiation that is emitted during alpha-decay, and the cellular oxygen independence of the affect of an alpha particle on the disease.
It has been shown that lead-212 (Pb-212) and astatine-211 (At-211) are effective in the treatment and eradication of microscopic carcinoma. The effectiveness of Pb-212 in treating the carcinoma is due to its subsequent decay to Bi-212, which is an alpha-emitting radionuclide. Pb-212, itself, is not as effective as the alpha-emitting Bi-212 radionuclide.
Known processes for producing alpha particle-emitting nuclides such as At-211 are limited in that they generally require the use of particle accelerators for production of the nuclides. Moreover, the radionuclides so produced are often contaminated with radio-impurities that are difficult to filter out or otherwise remove from a desired nuclide. It has also been found that such nuclides that are administered intraperitoneally using a complexing agent such as Pb-212/ferrous hydroxide do not have the desired property of even distribution.
Bismuth-212, which as noted above, is an alpha-emitting radionuclide, has recently been found to exhibit the desirable properties associated with At-211 in providing highly ionizing radiation and exhibiting cellular oxygen independence. Moreover, certain formulations of Bi-212 made in accordance with this invention as discussed hereinafter have also
REFERENCES:
patent: 2873170 (1959-02-01), Hyde et al.
patent: 3758663 (1973-09-01), Kirby
patent: 4663129 (1987-05-01), Atcher et al.
patent: 5030441 (1991-07-01), Atcher et al.
patent: 5038046 (1991-08-01), Norman et al.
patent: 5110474 (1992-05-01), Horwitz et al.
patent: 5772981 (1998-06-01), Govindan et al.
patent: 5817289 (1998-10-01), Klaveness et al.
Bloomer, McLaughlin, Neirinckx, Adelstein, Gordon, and Wolf, "Astatine-211 tellurim radiocolloid cures experimental ascites," Science, 212:340, 1981.
Dembo, "Abdominopelvic radiotherapy in ovarian cancer: a 10 year experience," Cancer, 55:2285, 1985.
Early, P.J. and Sodee, D.B. (eds.) In: Radiation measurement and protection, St. Louis, Missouri: Mosby, pp. 65-80, 1995.
Eastman Kodak Co., "Autoradiography at the light microscropic level," Kodak Tech. Bits, 1988.
Fisher, "The Microdosimetry of monoclonal antibodies labeled with alpha-particles," In: Fourth International Radiophrarmaceutical Dosimetry Symposium, A.J. Schlafke and E.E. Watson (eds.), U.S. Department of Energy, pp. 26-36, 1986.
Hall, E.J. (ed.) "Cell survival curves," In: Radiobilogy for the radiologist (4.sup.th ed.), Philadelphia, JB Lippincott Co., pp. 29-73, 1994.
Hartmann, Horak, Garmestani, Wu, Brechbiel, Kozak, Tso, Kosteiny, Gansow, Nelson, and Waldmann, "Radioimmunotheraphy of nude mice bearing a human interleukin 2 receptor .alpha.-expressing lymphoma utilizing the .alpha.-emitting radionuclide-cojugated monoclonal antibody .sup.212 Bi-anti-Tac," Canc. Res., 54:4362-4370, Aug., 1994.
Hartveit, The immediate cause of death in mice with ehrlich's ascites carcinoma, Acta Path. et al., Microbiol. Scandinav., 65:359-365, 1965.
Harvey, "Heavy metals," In: The Pharmacological Basis of Therapeutics, (3.sup.rd ed.), L.S. Goodman and A. Gilman (eds.), New York: McMillan Co., pp. 943-975, 1965.
Horwitz, E.P.: Dietz, M.L.; Rhoads, S.; Felinto, C.; Gale, N.H.; and Houghton, J.; "A Lead-Selective Extraction Chromatogrphic Resin and its Application to the Isolation of Lead from Geological Samples," Analytica Chimica Acta, 292 (3):263-273, 1994.
Huneke, Pippin, Squire, Brechbiel, Gansow, and Strand, Effective .alpha.-particle-mediated radioimmunotherapy of murine leukemia, Canc. Res., 52:5818-5820, Oct., 1992.
Junghan, Dobbs, Brechbiel, Mirzadeh, Raubitschek, Gansow, and Waldmann, Pharmacokinetics and bioactivity of 1, 4, 7, 10-tetra-azacylododecane N, N', N", N'"-tetraacetic acid (DOTA)-bismuth-conjugated anti-conjugated anti-tact antibody for .alpha.-emitter (.sup.212 Bi) therapy, Canc. Res., 53:5683-5689, Dec., 1993.
Kozak, Atcher, Gansow, Friedman, Hines, and Waldmann, "Bismuth-212-labeled anti-tac monoclonal antibody: .alpha.-particle-emitting radionuclides as modalities for radioimmunotherapy," Proc. natl. Acad. Sci. U.S.A., 83:474-478, Jan., 1986.
Loevinger, R., Budinger, T.F., and Watson, E.E. (eds.) "Primer part 1, MIRD primer for absorbed dose calculations," Soc. of Nucl. med., new York, Jan. 22, 1988.
rotmensch, Atcher, Hines, Grdina, Schwartz, Toohill and Herbst, "Development of d-emitting radionuclide lead-212 for the potential treatment of ovarious carcinoma," Am. J. Obstet. Gynecol., 60:789-797, 1989.
Rotmensch, Atcher, Hines, Toohill, and Herbst, "Comparison of short-lived high-LET .alpha.-emitting radionuclides lead-21 '2 and bismuth-212 to low-LET x-rays on ovarian carcinoma," Gynecol Onvol., 35:297-300, 1989.
Schwartz, Shadley, Atcher, Tang, Whitlock, and Rotmensch, "Comparison of radon-daughter-induced effects of repair proficient and repair deficient CHO cell lines," Environ. Mol. Mutagen. 16:178-184, 1990.
Selman, "Medical use of radionuclides," In: The Basic Physics of Radiation Therapy, (2.sup.nd ed.), Charles C. Thomas, Publisher, Springfield, Illinois pp. 472-533, 1976.
Shadley, Whitlock, Rotmensch, Atcher, Tang, and Schwartz, "The effects of radon daughter .alpha.-particle irradiation in K1 and xrs-5 CHO cell lines," Mutation Res., 248:73-83, 1991.
Simonson, Ultee, Hauler, and Alvarex, "Radioimmunotherapy of peritoneal
Harper Paul V.
Hines John J.
Rotmensch Jacob
Whitlock Jenny L.
ARCH Development Corporation
Mai Ngoclan
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