Oak Ridge Revives Rhenium-188 Generators for Prostate Cancer Research

Oak Ridge National Laboratory (ORNL) has resumed fabrication of tungsten-188/rhenium-188 isotope generators for the first time since 2011, restoring a domestic supply chain for a versatile medical isotope. The generators, produced for the National Isotope Development Center (NIDC) with funding from the Department of Energy's Isotope R&D and Production program, allow researchers to separate rhenium-188 (Re-188) from its parent isotope tungsten-188 (W-188) as needed. W-188 is created by irradiating tungsten-186 in ORNL's High Flux Isotope Reactor, and its 60-day half-life permits generators to be shipped globally and used for up to 18 months.

Associate radiochemist Becca Hoerres led the effort to modernize the generator design, replacing complex custom glass components with a simpler, less expensive column that can be operated in a standard fume hood rather than a specialized hot cell. The updated design aims to make the isotope more accessible for preclinical and clinical trials. ORNL already supplies W-188 to a European radiopharmaceutical company for an approved skin cancer treatment, but the new generators will allow NIDC customers to produce Re-188 on-site for a wider range of investigations.

The first recipients of the revived generators were researchers at Vanderbilt University School of Medicine. Graduate student Haswitha Sabbineni, working with professor Nancy Carrasco, is testing a gene-transfer strategy that uses a modified sodium/iodide symporter (NIS) protein to deliver Re-188 to prostate tumors. Carrasco's lab cloned the NIS gene in 1996, enabling radioiodide therapy for thyroid cancer; colleague Alejandro Llorente-Esteban later engineered an NIS variant that transports perrhenate (containing Re-188) but not iodide, allowing targeted treatment of non-thyroid cancers without harming the thyroid.

Sabbineni delivers the engineered NIS to prostate tumors in mice using nanoparticles called polyplexes, then administers perrhenate with Re-188 intravenously. The beta-emitting isotope has a short half-life and can penetrate tissue deeply, potentially destroying tumors while limiting damage to healthy cells. After receiving the ORNL generator and eluting Re-188 with remote guidance from Hoerres, the team observed that the treatment appeared to destroy tumors in mice without apparent negative effects elsewhere in the body. Sabbineni described the preliminary results as promising.

The generator housed at Vanderbilt is expected to last long enough for further preclinical testing. If successful, the approach would require additional Re-188 generators for clinical trials and could be extended to other cancer types. Hoerres noted that demand for the generators has grown and that ORNL plans to scale up production, including higher-activity versions, to support expanding research applications. The lab's ability to produce the parent isotope, fabricate the generator, and collaborate on medical applications represents a complete domestic pipeline for this isotope.