The Tungsten-188/Rhenium-188 Generator System and Development and Clinical Evaluation of Rhenium-188-Labeled Therapeutic Agents
We optimized the reactor production and processing of tungsten-188 and have developed the alumina-based adsorbant-type tungsten-188/rhenium-188 generator system and developed and patented new improved methods for the concentration of rhenium-188 bolus solutions to very high specific volumes. Because of the long physical half-life of the tungsten-188 parent (69 days) and the long useful generator shelf-life of several months with consistently high rhenium-188 yields (>75-80 % at equilibrium), this generator system holds great promise in providing the cost-effective rhenium-188 radioisotope for routine use for a variety of therapeutic applications. An important aspect of using rhenium-188 for many applications in contrast to other therapeutic radioisotopes is the anticipated very low costs for unit-dose, which would contribute to the reduction of health care costs. The tungsten-188/rhenium-188 generator is a major medical radioisotope distributed for routine sale through the ORNL Isotope Business Office.
Several collaborative clinical programs are evaluating our rhenium-188-labeled phosphonates for bone pain treatment, and Phase I studies with the rhenium-188-labeled HEDP and Re(V)-DMSA agents have shown specific targeting of skeletal metastases in patients presenting with metastases from various cancers (See Clinical Trials section). Protocols have also been developed initially with collaborators at Columbia University and Cedar Sinai Medical Center in Los Angeles for clinical evaluation of new rhenium-188 agents for inhibition of restenosis following coronary angioplasty. Protocols have also been developed for use of particles for arthritis therapy and tumor-specific antibodies for radioimmunotherapy.
We have also worked closely with the Nuclear Medicine Section at the International Atomic Energy Agency (IAEA) as a Research Agreement Holder for the design and implementation of the use of rhenium-188 for three major multi-center clinical trials involving the use of rhenium-188 for restenosis therapy following PTCA, for a new therapeutic strategy for therapy of refractory liver cancer and for radionuclide synovectomy. The tungsten-188/rhenium-188 generator is expected to have an important role in the developing world in providing rhenium-188 as a cost-effective therapeutic radioisotopes for a variety of applications because of the long useful shelf-life of several months.