Pair production tomography enables imaging of MeV-scale gamma-emitting theranostic radionuclides

High-energy gamma-emissions significantly degrade image quality when imaging theranostic cancer radiopharmaceuticals with conventional SPECT scanners, especially at low activities used in targeted alpha therapy. PET imaging offers sensitivity and energy discrimination benefits, but is conventionally limited to positron-emitting isotopes. Pair production tomography (PPT) addresses this limitation by enabling localization of high-energy γ rays: when a γ ray with energy ≥ 2mec2 (1.022 MeV) undergoes pair production, it generates an e+e− pair, and the positron subsequently annihilates, emitting two coincident 511 keV photons that can be detected for tomographic reconstruction. In this work, we present the first experimental demonstration of PPT in the context of 212Pb targeted alpha therapy, using 2.617 MeV γ rays emitted from its decay daughter 208Tl. 212Pb-filled phantoms were successfully imaged through PPT using time-of-flight clinical and non-time-of-flight preclinical PET systems, with SPECT images acquired for comparison. Monte Carlo simulations further support the experimental data and PPT mechanism. These findings establish the feasibility of PPT imaging for high-energy γ-emitters and motivate improvements in timing, reconstruction, and detector technologies for novel radiopharmaceutical imaging.