Background: Theranostics combines diagnosis and therapy in a single targeting moiety, with the modality determined by the chosen radionuclide. For diagnosis, positron emission tomography imaging uses positron-emitting radionuclides such as gallium-68 and fluorine-18. For therapy, beta-emitting radionuclides like lutetium-177 (177Lu) and alpha-emitting radionuclides such as lead-212 (212Pb) are employed. Alpha therapy with 212Pb is advantageous because as it’s produced onsite with generators, and a half-life of 10.6 hours aligning well with the biological half-life of many peptide-based targeting vectors that are often used to deliver the cytotoxic payload to tumours. 212Pb presents unique activity-measurement challenges not encountered with conventional isotopes such as 177Lu. It exists in an equilibrium with decay products bismuth-212, polonium-212, and thallium-208 so calibrations are based on this equilibrium rather than on 212Pb alone. Chemical processing separating these components can disturb the equilibrium, complicating radioactivity measurements and dose calibration.
Methods: We developed a gamma spectroscopy approach using a NaI detector to map decay-product distributions when out of equilibrium. After calibrating the detector to the equilibrium system, the proportion of daughter products after any disturbance may be determined by comparison to the known equilibrium spectrum due to daughter photon emissions. We determined correction factors for accurate radioactivity measurements with standard ionization chambers for any equilibrium state.
Results: This approach addresses a key limitation in radiopharmacy, improving safety, efficacy, and reproducibility, and can be adapted to other isotopes with similar dynamics. Considerations include workflow integration, cross-validation across platforms, regulatory implications, and broader applicability to manufacturing and clinical settings.
Conclusion: A gamma spectroscopy–based method using a NaI detector determines out-of-equilibrium decay distributions and derives correction factors for precise measurements with standard detectors, enabling reliable analysis, calibration, and quality control of 212Pb across equilibrium states. This supports robust dose quantification and may better facilitate clinical translation of 212Pb-based theranostics.