PNNL

Abstract

This report summarizes the development and demonstration of thorium-228/radium-224/radon-220 (228Th/224Ra/220Rn) and radium-224/radon-220 (224Ra/220Rn) emanation-based generator for producing high-purity 212Pb in a form suitable for targeted alpha therapy applications. The project was motivated by limitations of conventional wet-column 224Ra/212Pb generators, including the possibility of 224Ra breakthrough and the need for post-elution chemical processing prior to biomolecule labeling. In contrast, the approach described here uses gas-phase transport of 220Rn away from a 228Th or 224Ra-bearing source, followed by spatially separated decay to 212Pb and aqueous recovery of the product into a radiolabeling-compatible buffer solution. The work addressed the five original Specific Objectives, while accounting for the later revised scope in which no tasks were eliminated, but several activities were reduced in scale. The team identified practical 220Rn emanation source configurations based on a suite of commercially available resins and specific carrier gas conditions. The project also evaluated multiple Rn collection strategies, including organic solvent capture, cryogenic deposition, organic nanocage media (CC3), and closed-loop decay chamber concepts. These studies established the basis for a simplified generator approach in which 220Rn is transported from the source and 212Pb is subsequently recovered from the collection region in small aqueous volumes. A major outcome of the report is the demonstration that the generator can produce 212Pb with high yields, purity, and chelation performance. The decay chamber concept enabled recovery of most chamber-deposited 212Pb into ammonium acetate or sodium acetate buffers. Generator testing used both 228Th and 224Ra emanation sources; the highest-activity generator testing reached approximately 18.7 mCi, exceeding the revised 10–15 mCi activity target. In these evaluations, 212Pb recovery into sodium and ammonium acetate was typically near 90% of the decay chamber activity, with overall product yields (considering 220Rn emanation fraction and 212Pb collection fraction) reaching approximately 82% under the best conditions. Product purity was likewise strong: decay-based measurements showed no detectable 228Th or 224Ra contamination in selected high-activity product fractions, with calculated 212Pb product decontamination factors greater than 108. Results also demonstrate that the recovered 212Pb product is chemically useful, not merely radionuclidically pure. When 212Pb was collected directly into ammonium acetate containing the TCMC (DOTAM) chelator, essentially quantitative complexation was observed, with 99.8–100.0% bound and 99.3–99.7% bound when assessed by an instant thin layer chromatography (iTLC) and aminopropyl (NH2) cartridge method, respectively. These results indicate that the product matrix did not contain a bindable-metal inventory sufficient to inhibit TCMC labeling under the evaluated conditions. We also demonstrated that radiolabeling onto TCMC chelator can happen concurrently with 212Pb stripping with acetate salt solutions – thereby reducing 212Pb collection and labeling to a single step. Overall, the report shows that the revised project objectives were met: the team developed an automated, high-yield 228Th/212Pb and 224Ra/212Pb generator concept capable of producing high-purity, label-ready 212Pb while substantially reducing the risk of parent-isotope breakthrough and opportunities for metals contamination. Finally, the project trained future radiochemists by embedding students and Research Associates directly into the full development cycle of the generator system. Participants gained hands-on experience in alpha-emitting radionuclide handling, source preparation, gas-phase 220Rn transport, generator assembly, automated fluidic operation, radiometric counting, decay correction, yield calculations, radionuclidic purity assessment, contamination control, and radiol