1. Field of the Invention
This invention relates to methods, apparatus and compositions for separating yttrium-90 from strontium-90.
2. Background of the Related Art
The use of radioactive isotopes as diagnostic, imaging and therapeutic agents is a relatively new area of medicine that has flourished in the last fifty years. A number of radioisotopes, primarily beta emitting radionuclides, are finding use in the in vitro treatment of cancers to destroy or sterilize cancer cells. The treatment is administered in a series of cycles to avoid radiotoxicity to other areas of the body, particularly the kidneys and bone marrow. The isotopes of interest are commonly attached to monoclonal antibodies specific for the cancer cells to be treated, thus delivering a dose of radiation directly to a tumor. This technique is termed radioimmunotherapy (RIT) and is increasingly being used to complement existing surgical techniques and chemotherapy.
In order to fuel the current research in the use of radionuclides to treat cancers, it is essential that new isotope production methods be developed to increase the availability and decrease the cost of radioisotopes. For medicinal applications, the radioisotope supplied needs to be radiochemically pure to prevent the accidental introduction of unwanted additional radionuclides into a patient, and, preferably, be carrier free. A fundamental aspect of increasing the availability of radioisotopes to medical personnel is the development of new, inexpensive, radiolytically stable materials to allow the necessary separations to be achieved.
90Y is a high-energy beta emitter that is finding use in the treatment of certain forms of cancer. 90Y decays by pure beta emission, with a half-life (T1/2) of 64 hours, to stable 90Zr. The energetic beta particles (2.3 MeV) can penetrate an average of 0.5 cm in human tissue, with a maximum penetration of up to 1 cm. Consequently, they are useful in the treatment of cancerous tumors like those found in Hodgkin's disease, where tumors are typically between 1 and 5 cm in diameter. The 90Y can be successfully attached to an antibody, which will then transport the 90Y to the targeted tumor.
In order to use 90Y in the treatment of cancers, it is necessary to obtain a very pure source of the isotope that is free from the parent 90Sr. This is essential because 90Sr has a 28 year half-life and is likely to accumulate in the bone if inadvertently introduced into the body. The maximum tolerable amount of 90Sr fixed in the bone is only 2 μCi and consequently great care needs to be performed to achieve the necessary Sr/Y separation to ensure minimal introduction of 90Sr into the body during the 90Y radiotherapy.
90Y is the daughter product of 90Sr, an abundant fission product of 235U, found in nuclear wastes resulting from the reprocessing of spent commercial nuclear fuel and in the separation of 239Pu for weapons manufacture. 90Sr has a half-life of approximately 28 years. The radioactive decay scheme is outlined in Equation 1 below.90Sr(β−)→90Y(β−)→90Zr  (1)
In order to obtain a supply of 90Y, it is first necessary to separate 90Sr from other isotopes in the nuclear waste. This can readily be achieved using selective precipitation, ion exchange or solvent extraction techniques to produce a crude 90Sr ‘cow’ for use as a source of 90Y. 90Y can also be produced by the neutron irradiation of 89Y oxide, Y2O3, for a period ranging from several days to a week, but this is expensive and the 90Y product contains large amounts of inactive 89Y, making it unsuitable for medicinal applications.
There are a number of methods described in the literature for the separation of the 90Y daughter from the parent 90Sr, including solvent extraction, ion exchange, precipitation and chromatographic procedures. Of these methods, ion exchange techniques have probably received the most attention. However, all of the current methods suffer from drawbacks. For instance, in some separation procedures, the 90Sr is held onto an organic cation exchange resin and the 90Y is eluted using an aqueous complexant solution, such as EDTA, oxalate, lactate, citrate etc. Consequently, the purified 90Y is generated as a complex that is not suitable for the direct labeling of antibodies and requires further processing. Organic ion exchange resins are also prone to radiation damage resulting in a decrease in capacity and the potential release of toxic organic molecules into the 90Y stream as the resin decomposes. Consequently, there is a need for new material and methods to produce pure 90Y.
The method disclosed by Bray and Webster in U.S. Pat. No. 5,512,256 uses a solvent extraction process to separate 90Y from 90Sr. A 0.3M solution of di(2-ethylhexyl)phosphoric acid (HDEHP) in n-dodecane is used to extract 90Y from a solution of 90Sr/90Y in 0.3M nitric acid. The HDEHP selectively extracts the 90Y into the organic phase and residual 90Sr can be removed by further washing the organic fraction with fresh 0.3M nitric acid. Although this method is very effective at separating 90Y from 90Sr, multiple steps are required and the recovery of both the 90Sr cow and 90Y fractions requires multiple washing and stripping phases. This produces waste organic and aqueous streams that need to be treated and disposed of safely. There will also be some radiolysis of both the organic complexant and the solvents that will limit their useful life and also may cause the release of unwanted organic species into solution. This is the primary method utilized to produce 90Y in the USA today.
In U.S. Pat. No. 5,368,736, Horwitz and Dietz use a multiple step chromatographic process to separate 90Sr from 90Y. The 90Sr stock solution in 3M nitric acid is passed through three strontium selective chromatographic ion exchange columns in series so that the solution exiting the third column contains essentially only 90Y, the 90Sr being retained on the columns. This raw 90Y solution is the passed through a rare earth selective column that selectively extracts the 90Y. The purified 90Y can then be eluted off the column. However, the chromatographic columns contain organic resins that are susceptible to radiation damage and may leach undesirable radiolysis fragments into the purified 90Y stream. Radiation damage is kept to a minimum by loading and then eluting the radioactivity from the columns, but this method also requires the use of a dedicated hot cell facility, necessitating shipment of the purified 90Y to the end user.
Huntley's U.S. Pat. No. 5,494,647 discloses an ion exchange process for separating 90Y from 90Sr using CHELEX-100® (Bio-Rad Laboratories, Richmond, Calif.), a chelating ion exchange resin. CHELEX-100® is an organic ion exchange resin that consists of iminodiacetic acid groups mounted on a polystyrene/divinyl benzene substrate. The method is designed for use with environmental samples only containing trace amounts of 90Sr, and it is disclosed that the method does not work effectively at high strontium concentrations. The organic resin would also be susceptible to radiation damage and it is doubtful that the method would be able to produce the level of 90Y purity required for medicinal applications.
Therefore, there is a need for improved methods, apparatus, and compositions for separating yttrium-90 from strontium-90. It would be desirable if the compositions were highly radiation resistant, thermally stable, chemically stable, and non-toxic. It would be even more desirable if the compositions and methods provided very high affinities for strontium-90 and very low affinities for yttrium-90.