Advances in Dosimetry and Imaging for 203Pb and 212Pb Radiotheranostics.

Abstract

Targeted alpha therapy (TAT) with ²¹²Pb is rapidly emerging as a potent modality for cancer treatment due to the high linear energy transfer and short path length of α-particles, which enable precise tumor cell killing while sparing surrounding healthy tissue. Its elementally identical theranostic partner, ²⁰³Pb, functions as a γ-emitting surrogate for quantitative SPECT imaging, providing essential information for patient-specific dosimetry and treatment planning. Advances in SPECT imaging, ranging from NaI(Tl)-based dual-head systems to CZT multi-detector gamma cameras, have enhanced spatial resolution, quantitative accuracy, and lesion detectability, enabling rapid patient scanning and improved activity quantification for dosimetry. Clinical dosimetry workflows that integrate serial ²⁰³Pb SPECT/CT acquisitions, pharmacokinetic modeling, and image-based activity quantification facilitate reliable generation of time-activity curves and absorbed dose estimates. Organ-level and voxel-based dosimetry, combined with advanced reconstruction and microdosimetric modeling, further refine dose calculations, supporting individualized therapy planning. Collectively, these developments highlight the translational potential of the ²⁰³Pb/²¹²Pb theranostic pair. The aim of this review is to provide a comprehensive assessment of ²¹²Pb-TAT, encompassing clinical applications, surrogate imaging with ²⁰³Pb, gamma camera performance, dosimetry workflows, and predictive activity quantification, illustrating how these advances collectively enable quantitative, patient-specific, and theranostic-integrated radionuclide therapy.