Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Coated – impregnated – or colloidal particulate
Reexamination Certificate
1999-02-01
2002-04-30
Dudash, Diana (Department: 1619)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Coated, impregnated, or colloidal particulate
C424S001370, C424S489000, C424S490000, C424S451000, C424S457000, C600S003000, C501S033000, C501S052000, C252S644000
Reexamination Certificate
active
06379648
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to radiation therapy such as radiation synovectomy of arthritic joints and biodegradable glass compositions in particulate form for use in radiation therapy.
Currently, no material for the in vivo delivery of therapeutic doses of beta radiation have been approved for use in the United States for irradiation of diseased organs in the body, e.g. malignant tumors and the inflamed synovium of arthritic joints. Materials that have been investigated previously for in vivo radiotherapy can be classified as bio-inert (non-degradable) glasses (e.g. Ehrhardt et al. Nuc. Med. Biol., 14 [3] (1987); Ehrhardt et al., Soc. of Nuc. Med., 39th Annual Meeting, June 9-12 (1992); Day et al., Advanced Series in Ceramics—Vol. 1, p. 305-317, World Scientific (1994); Hyatt et al., J. Am. Ceram. Soc., 70 [10] (1987); and Erbe et al., J. Biomed. Mat. Res., 27, 1301-1308 (1993)) or non-glasses (e.g. Ansell, Ann. Rheum. Dis., 6 Supp. 1-2 (1993); Ingrand, Ann. Rheum. Dis., 6 Supp. 3-9 (1973); Boerbooms et al., Eur. J. Nuc. Med., 10 (1985); Spooren et al., Eur. J. Nuc. Med., 10 (1985); and Neves et al., Appl. Rad. Isat., 38 [9] (1987)). All of these materials can be administered to the patient by injection in a similar fashion.
Bio-inert radiotherapy glass particulates have already demonstrated the effectiveness of glass materials for safely delivering large localized does of therapeutic beta radiation. However, such glasses are limited to therapies where the glass can remain in the body indefinitely. Radiation synovectomy of diseased joints is one example of an application where the eventual removal (clearance) of the radiopharmaceutical may be desired. This creates the need for a biodegradable material.
Non-glass materials that have been proposed for use as radiopharmaceuticals include radiocolloids and ceramic, polymer or protein particulates that have a radioactive isotope attached (bonded) to their surface. Several of these non-glass materials can be cleared from in vivo treatment sites such as a rheumatoid arthritic joint. Each has shortcomings, however, that limits their usefulness and safety during preparation and use. These shortcomings include: (1) release of excessive or potentially dangerous amounts of radiation outside the treatment site. This unwanted release has occurred due to the physical escape of the intact radioactive materials, the disintegration of the materials into smaller particles or ionic species while still radioactive, or the “debonding” of the radioisotope from the surface of a particle when in contact with body fluids; (2) the radiation dose is limited to amounts smaller than desired for certain applications; (3) complex preparation procedures that include handling radioactive substances during fabrication; and (4) use of radioisotopes with a short half life, which means that the material must be used quickly. This limits the time available for distributing (mailing) the radiopharmaceutical and causes other inconveniences.
Beta-emitting radionuclides are considered the most useful for radiotherapeutic applications because of the moderate linear energy transfer (LET) of the ionizing particle (electron) and its intermediate range (typically several millimeters in tissue). Gamma rays deliver dosage at lower levels over much greater distances. Alpha particles represent the other extreme; they deliver very high LET dosage, but have an extremely limited range and must, therefore, be in intimate contact with the cells of the tissue to be treated. In addition, alpha emitters are generally heavy metals, which limits the possible chemistry and presents undue hazards from leakage of radionuclide from the area to be treated.
It is fortuitous that beta emitters, the most useful radiotherapeutic radionuclides, are also the ones most copiously produced by neutron capture in nuclear reactors, the most powerful sources of radioisotopes. Reactor-produced isotopes number in the thousands, giving researchers a wide choice of isotopes of various half-lives, beta energies, gamma emissions, and chemical properties. Gamma emissions, while not as useful as beta emissions, play an important role in that they permit the distribution of radioisotope in the body to be observed using an Anger gamma ray camera or single photon computed tomography (SPECT) instrument. This permits direct observation and, to some extent, quantification of radionuclide leakage from an organ or a joint and also provides positive verification of the potency of joint injection and distribution of the radionuclide in the research animal.
With respect to radiation synovectomy of arthritic joints, treatment of the different depths of diseased synovium in joints of disparate size, such as the finger joints and the knee, requires isotopes of different average beta range. It is important to achieve a “kill” of sufficient depth to be efficacious without causing significant necrosis of overlying normal tissues.
Rare earth containing glass microspheres have been considered for radiation synovectomy treatment of rheumatoid arthritic joints. The radioactive glass microspheres could be injected directly into the synovial sac and deliver enough radiation (≧10,000 rads (cGy)) to destroy the inflamed lining of the diseased synovial membrane. Radiocolloid particulates, e.g.
90
Y or
198
Au salts, are presently used in Europe for radiation synovectomy (e.g. Houle et al., Radiology 172 [3] 1989); Russel et al., Endocurietherapy/Hyperthermia Oncology, 4 [7] 171-186 (1988); Sledge et al., Arth. Rheum. 29 [2] 153-159 (1986); Davis et al., J. Nucl. Med., 30 [6] 1047-1055 (1989); Hall, Orthop. Clin. North Am., 6, 675-684 (1975); and Taylor et al., Ann. Rheum. Dis., 31, 159-161 (1972)), but have not been approved for use in the United States because of unacceptable amounts of radiation leakage during their use. The radiocolloids are known to easily escape the synovium due to their sub-micron size, and in certain instances 25% of the targeted radiation has been deposited in healthy tissue outside the joint. Glass microspheres for radiotherapy are much larger (>1 &mgr;m in diameter) than the radiocolloids and have the additional advantage of a carefully controlled size within a few microns.
U.S. Pat. No. 5,011,797 dated Apr. 30, 1991 discloses radioactive microspheres for radiation synovectomy of arthritic joints which comprise a biodegradable glass material and a beta radiation emitting radioisotope chemically dissolved in and distributed substantially uniformly throughout the glass material. The biodegradable glass material may be lithium silicate, lithium aluminosilicate, lithium aluminoborate, lithium germanate, lithium aluminogermanate, potassium silicate, potassium aluminosilicate, potassium aluminoborate, potassium germanate or potassium aluminogermanate and the beta radiation emitting radioisotope may be samarium-153, holmium-166, erbium-169, dysprosium-165, rhenium-186, rhenium-188 or yttrium-90. The patent also discloses non-biodegradable glass materials such as magnesium aluminosilicate and aluminosilicate glass materials which contain a beta radiation emitting radioisotope.
There is a continuing need for improved glass materials adapted for radiation therapy such as radiation synovectomy of arthritic joints.
SUMMARY OF THE INVENTION
Among the several objects of the invention may be noted the provision of novel biodegradable rare earth-lithium borate glass materials for use in radiation therapy; the provision of such glass materials containing beta or gamma emitting radioisotopes; the provision of such glass materials in the form of microspheres; the provision of such biodegradable glass materials which upon being introduced into a body fluid for radiation therapy are adapted to react therewith causing the radioisotope contained therein to react with the body fluid causing the radioisotope to form an insoluble compound on the surface of the glass material which is retained on the glass material and thereby prevented f
Day Delbert E.
White James E.
Dudash Diana
Senniger Powers Leavitt & Roedel
Sharareh S
The Curators of the University of Missouri
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