This invention relates to radiolabeled protein compositions being adaptable for radiation therapy, diagnosis and research. The invention also relates to a method of using protein microspheres for radiation synovectomy.
It is estimated that 1-3% of the population in the United States has rheumatoid arthritis (hereinafter RA), which can cause chronic synovial inflammation and can lead to progressive loss of joint function and significant disability. RA has heretofore been treated primarily by surgical or chemical synovectomy. Surgical synovectomy consists of the surgical removal of the inflamed lining of the joint (synovium), and in general can be expected to provide limited periods of symptomatic relief. It is technically difficult, however, to completely remove the synovium from the joint. Surgical synovectomy entails risks such as infection, hemorrhage and anesthetic problems. Surgery often requires prolonged periods of hospitalization and rehabilitation for recovery. Surgery is expensive, invasive and is not attractive for repeat treatments. Proposed methods of chemical synovectomy use osmic acid, cobra venom or other agents and often have significant systemic effects such as injury to the articular cartilage.
Radiation synovectomy has been proposed, for example, by Johnson et al., Absorbed Dose Profiles for Radionuclides of Frequent use in Radiation Synovectomy, Arthritis and Rheumatism, Vol. 34, No. 12, p. 1521 (Dec. 1991), for the treatment of RA and offers a viable alternative to surgery and chemical synovectomy. Radioisotopes are commonly used for research, treatment and diagnosis in the field of nuclear medicine. Such applications include liver, lung, bone and tumor scanning and radiotherapy. Radiation synovectomy radiotherapy involves delivering a lethal dose of beta radiation to diseased synovial membrane.
Radiation synovectomy has been used in Europe but certain disadvantages have made it generally unacceptable for use in the United States. Radiation synovectomy treatments in Europe have employed yttrium-90 radiocolloids which emit beta radiation but do not emit gamma radiation. It has therefore not been possible to track radiation leakage and the spread of radioactivity within the patient using an external gamma ray detector. Additionally, prior methods of radiation synovectomy often suffer from high radioactivity leakage rates of the particulate preparations which serve as carriers for the radioactivity. Radiation synovectomy treatments have therefore lacked the ideal source of radiation and the ideal radioactivity carrier.
Microspheres formed from human serum albumin have been proposed for use as radioactivity carriers in connection with the use of radioactivity for diagnostic purposes, e.g., lung scanning, as in Radiopharmaceuticals, Soc'y Nuc. Med., p. 282, New York (1980). Specifically, human serum albumin microspheres have been radiolabeled with Tc-99m and injected or otherwise allowed to enter a mammalian host. A gamma ray detector has then been used to image certain areas of the patient. Microspheres labeled with Tc-99m, however, are not suitable for radiation therapy, and radiation synovectomy treatment for RA in particular; Tc-99m emits gamma radiation, not the beta radiation which is lethal to diseased synovial membrane.
Accordingly, a need has existed for an improved method and materials, including radioisotope carrier, for use in radiation synovectomy treatment of RA. A need has also existed for an improved radioisotope carrier for use in research, treatment and diagnosis in the field of nuclear medicine.
USPTO Backgrounds
USPTO Backgrounds