Description: Separation from contaminants and bulk material and purification to customer specifications are critical processes in the production cycle of an isotope. Many production strategies and techniques used presently rely on old technologies and-or require a large, skilled workforce to operate specialized equipment, such as manipulators for remote handling in hot cell environments. Conventional separation methods may include liquid-liquid extraction, column chromatography, electrochemistry, distillation or precipitation and are used to separate radioactive and non-radioactive trace metals from target materials, lanthanides, alkaline and alkaline earth metals, halogens, or organic materials. High-purity isotope products are essential for high-yield protein radiolabeling, for radiopharmaceutical use, or to replace materials with undesirable radioactive emissions. Improved product specifications and reduced production costs can be achieved through improvements in separation methods. Of particular interest are developments that automate routine separation processes in order to reduce operator labor hours and worker radiation dose, including radiation hardened semi-automated modules for separations or radiation hardened automated systems for elution, radiolabeling, purification, and dispensing. Such automated assemblies should be easily adaptable to different processes and hot cell use at multiple sites, including the DOE laboratories currently producing radioisotopes.
Although, PET-style equipment (cyclotrons and fluid target systems) using automated chemistry modules are increasingly available, they are generally underutilized. Employing this equipment to supplement commercial production of PET products with additional newer radioisotopes (e.g., Zr-89, Pb-203, Tc-94m), as well as, existing radioisotopes (e.g., I-124, Cu-64, I-111) would be a synergistic and efficient use of resources. Applications are sought for developing commercial methods similar to and compatible with existing commercial PET production method.
Applications are sought for innovative developments and advances in separation technologies to reduce processing time, to improve separations efficiencies, to automate separation systems, to minimize waste streams, and to develop advanced materials for high-purity radiochemical separations. In particular, the Department seeks breakthroughs in lanthanide and actinide separations. Incremental improvements are also encourage, such as (1) in the development of higher binding capacity resins and adsorbents for radioisotope separations to decrease void volume and to increase activity concentrations, (2) the scale-up of separation methods demonstrated on a small scale to large-volume production level, and (3) new resin and adsorbent materials with increased resistance to radiation, and with greater specificity for the various elements.
The following are some new strategies for radioisotope processing and separation technologies. In lanthanide radiochemistry, improvements are sought to a) prepare high-purity samarium-153 by removing contaminant promethium and europium; or b) to prepare high-purity gadolinium-148 and gadolinium-153 by ultra-pure separation from europium, samarium, and promethium contaminants. Sn-117m has gotten a lot of interest in the last few years. It has favorable nuclear properties for both imaging and therapy. However commercial quantities of the isotope at high specific activity are not available. Supply of commercial quantities of high specific activity Sn-117m would be of high interest. Re-186 has excellent nuclear properties for therapy and is chemically similar to Tc-99m which is widely used for diagnostic imaging. Therefore, Re-186 could be used as a therapeutic matched pair for currently available diagnostic imaging agents. However, high specific activity Re-186 is not available. So, alternative methods of production or mass separation to remove stable Re isotopes, which can provide commercial quantities of high specific activity Re-186 are highly desirable. In actinide radiochemistry, innovative methods are sought a) to improve radiochemical separations of or lower-cost approaches for producing high-purity actinium-225 and actinium-227 from contaminant metals, including thorium, radium, lead, lanthanides, and-or bismuth; or b) to improve ion-exchange column materials needed for generating lead-212 from radium-224, and bismuth-213 from actinium-225 and-or radium-225. The new technologies must be applicable in extreme radiation fields that are characteristic of chemical processing involving high levels of alpha-and-or beta--gamma-emitting radionuclides.
Recent advances in translation and clinical trials of alpha-particle mediated therapies have focused attention on the production and purification of long lived parent radionuclides for radium-223 and lead-212 production. Regulatory approval for the treatment of metastatic bone cancer originating from advanced prostate cancer using radium-223 dichloride has been obtained from the US Food and Drug Administration and initial phase I clinical trials of lead-212-TCMC-Trastuzumab for treatment of HER-2 expressing carcinoma (e.g., ovarian, pancreatic, peritoneal), are currently being conducted in the US. However sufficient amounts of the parent isotopes are not available to support full clinical implementation. Innovative methods are sought for 1) the production of actinium-227 and thorium-228, 2) the purification of actinium-227 and thorium-228 from contaminating target materials and decay chain daughters, and 3) the generation of high specific activity radium-223 and lead-212 for clinical applications