Various techniques have been developed to treat tumors in the body. In general, the use of radiation as a means to reduce or eliminate malignancy has been known for many years.
The type of radiation treatment of malignant tumors often performed involves directing a beam of radiation from a point external to the patient's body onto the area of the body in which the tumor is located, for the purpose of shrinking and ultimately destroying the tumor. This technique is known as “teletherapy” or external beam radiation therapy. Such treatment exposes normal healthy tissue to the high dosage of radiation in the beam and consequently subjects this normal healthy tissue to potential injury.
Brachytherapy is a method of radiation treatment of cancerous tissue in which the radiation source is placed in or near the cancerous tissue. Brachytherapy treatment permits administration of higher radiation dose to the tumor while reducing the exposure of surrounding normal healthy tissues.
Brachytherapy came into use as a treatment tool for cancer soon after the discovery of radium by Marie Curie in 1898. Goldberg and London used it for the treatment of facial basal cell carcinomas in 1903 with surface applicators.
Failla, in U.S. Pat. Nos. 1,753,287 and 1,954,868, describes a method of fabricating sealed sources of radium and their use for therapeutically treating cancer or tumors or other diseases.
Brachytherapy can be applied to cancer either by permanent implantation or by temporary application of removable sources. A variety of radionuclides and methods for permanent implantation have been described.
Wappler, in U.S. Pat. Nos. 2,322,902 and 2,429,438, describes a method of manufacturing sealed sources of “radium emanation intended for implantation into a human body for the purpose of producing certain beneficial effects upon cancerous growths and the like.” Lawrence, in U.S. Pat. No. 3,351,049, describes the manufacture of permanently implantable seeds using 125Iodine, 131Cesium and 103Palladium. Packer, et al., in U.S. Pat. No. 3,438,365, describe the structure, method of manufacture, and use of seeds for implantation containing radioactive isotopes of xenon for use in cancer radiation therapy. Horowitz, in U.S. Pat. No. 4,815,449, describes a delivery system for implanting a plurality of seeds into living tissue in a predetermined array configuration.
Permanent implantation results in the radioactive sources, or seeds, being left in the body in perpetuity, delivering their radiation dose until the radioactive material in the source has completely decayed away. This is not appropriate for some patients.
Temporary brachytherapy is a process whereby the radioactive sources are placed into the body, usually using an applicator, such as a needle, catheter or other tubular apparatus, for a period of time to deliver the requisite radiation dose, following which the sources are removed. In general, applicators are prepositioned in the patient, and sources are later temporarily placed within them. This procedure is known in the field as “afterloading.”
Loftus, in U.S. Pat. No. 2,546,761, describes an applicator used to temporarily deliver the radiation from a radium source for the treatment of lymphoid tissue in the nasopharynx. Rush, in U.S. Pat. No. 3,060,924, describes an apparatus for temporarily applying radioactive substances within the body such as the cervical-vaginal cavities.
Originally, temporary brachytherapy was performed using a technique that became known as “low dose rate brachytherapy.” Using this technique, radioactive sources would be applied to provide a dose rate of 0.4 to 2 Gy/hour to the tumor. Using these techniques, treatment would require up to several days, during which period the patient would remain hospitalized. Low dose rate techniques utilized a variety of radioactive isotopes, including 125Iodine, 137Cesium, 198Gold and 192Iridium.
“High dose rate brachytherapy,” developed later, uses a source that provides dose rates in the range of 2-7 Gy/minute. This technique permits the treatment to be performed in less than an hour and without hospitalizing the patient. These treatments are typically delivered in multiple fractions over several days or weeks.
High dose rate brachytherapy is particularly appealing to facilities with large patient populations, where treatment by low dose rate brachytherapy would require prolonged hospitalizations. Treating these patients as outpatients, using multiple fraction treatment regimens of high dose rate brachytherapy, is appealing to the patients. Free-standing radiation therapy centers that do not provide hospital rooms also find high dose rate brachytherapy appealing.
Sauerwein, et al., in U.S. Pat. No. 3,669,093, describe an apparatus for performing high dose rate brachytherapy using an afterloading source. Van't Hooft, et al., in U.S. Pat. No. 4,881,937, describe a method for performing high dose rate treatment to a part of the body. Liprie, in U.S. Pat. No. 5,084,002, describes a high dose rate 192Iridium source for the treatment of cancer.
Current high dose rate brachytherapy is performed exclusively using 192Iridium sources which have an initial activity of ˜10 Curies. Such sources produce dose rates of 6.8 Gy/min at 1 centimeter. Using such a source, high dose rate treatments are typically performed for 5-15 minutes.
192Iridium sources can be readily produced from substantially pure iridium. Relatively small amounts of iridium (e.g., a small volume) can be irradiated to a relatively high level of radioactivity in a relatively small size. 192Iridium has been produced by prior art techniques in a nuclear reactor with dosages of up to 10 curies in a diameter small enough to allow a source wire diameter of about 1 millimeter (mm). Liprie describes one technique for achieving this in U.S. Pat. No. 5,395,300.
192Iridium sources have a significant disadvantage. 192Iridium sources emit very high energy gamma radiation, with principal energies in the range of 300-600 keV, and with some emissions in excess of 1000 keV. Consequently, these sources require an enormous amount of shielding. A typical 192Iridium treatment room requires more than 50 mm of lead shielding or 0.6 meters of concrete shielding to provide radiation protection to the clinical personnel and others in the vicinity of the treatment room. As a result, building a facility designed to use this type of source represents a very significant investment.
An exemplary radionuclide for the treatment of malignant tumors would emit x-rays and/or gamma rays with energy in the range of 50 keV to 70 keV, with little x-ray or gamma ray emission outside this range. This energy range will provide a favorable dose distribution surrounding a tumor, while enabling the source to be adequately shielded by a relatively thin amount (˜1 cm) of lead. 169Ytterbium meets this criterion.
The use of 169Ytterbium for the treatment of malignant tumors has been investigated before.
Mason, et al., in Medical Physics 19 (3) 695-703 (1992) describe the calculated physical properties of a 169Ytterbium source. They discuss the theoretical possibility of achieving sources with activity concentrations of 350 GBq/mm3 (<10 Ci/mm3). However, the authors report only theoretical results, and do not provide any data relating to achieving high activity in these sources.
Fisher, et al., in Endocurietherapy/Hyperthermia Oncology, 9, 195-199 (1993) describe the first clinical application of a 169Ytterbium low dose rate brachytherapy source.
Perera, et al, in International Journal of Radiation Oncology, Biology and Physics, 28 (4) 953-970 (1994) describe the dosimetric characteristics, air-kerma strength calibration and Monte Carlo simulation for a new 169Ytterbium brachytherapy source. The basis of the work of this paper was interstitial seeds used for low dose rate brachytherapy. However, the authors also describe an “experimental high dose rate source.” However, this source would not be considered a high dose rate brachytherapy source by current standards. It was significantly larger than the conventional high dose rate (HDR) sources in commercial use (2.5 mm in diameter vs. 1 mm in diameter for current high dose rate sources). This source was also much lower in activity than the typical sources currently used for high dose rate brachytherapy (86 millicuries vs. 10 curies for current high dose rate sources).
Das, et al., in Phys. Med. Biol., Vol. 40, pp 741-756, (1995) report on measurements of a HDR-type source. The actual activity of the source was not reported, but the HDR-type source was described as “low strength” and reference was made to 5-20 millicuries.
High activity 169Ytterbium sources have been produced for industrial use. Isotope Products, Inc. has registered a 169Ytterbium source with dimensions of 1 mm diameter and 3.6 mm length and a maximum activity of 5 curies. This source was much lower in activity than the typical sources currently used for high dose rate brachytherapy (10 curies).
MDS Nordion describes a 169Ytterbium source with an active diameter of 0.6 mm and length of 0.6 mm and a nominal activity of 1 curies and another with an active diameter of 1.0 mm and length of 1.0 mm with a nominal activity of 3 curies. These sources are also much lower in activity than the typical sources currently used for high dose rate brachytherapy (10 curies).
Thus, it would be desirable to have methods and materials for making 169Ytterbium available as a high dose rate temporary X-ray and gamma ray source. Such materials should be capable of being fabricated into sources small enough to fit in a delivery catheter, but with enough activity to enable therapy within a reasonable amount of time.
Such a method could provide a new and improved radioactive source for in vivo localized radioactive treatment of malignant tumors and could be exploited to provide high dose rates and a more favorable energy spectrum for better radiation protection properties and certain clinical benefits.
It is also desirable to provide an improved design and method of fabrication for a high dose radioactive source for use in interstitial, intraluminal and/or intracavitary brachytherapy.
It is also desirable to provide a radioactive source for treatment that is cost effective.
USPTO Backgrounds
USPTO Backgrounds