LAFOV PET/CT Detects 225Ac but Cannot Localize Activity Due to Distant Annihilations

The arXiv preprint from University of Bern tested whether pair production from the 1567 keV 209Tl gamma could enable standard clinical PET reconstruction of 225Ac. A syringe-vial setup and NEMA IEC phantom were imaged under routine acquisition parameters; FLUKA Monte Carlo scored annihilation positions around a point source, confirming exponential fall-off governed by the photon mean free path in water and tissue-equivalent material.

Targeted alpha therapy with 225Ac-DOTATATE or PSMA ligands requires accurate dosimetry, yet conventional SPECT lacks sensitivity for the low-yield 218 keV and 440 keV lines. The present data indicate that annihilations occur centimeters from the decay site, violating the line-of-response assumption fundamental to PET and rendering quantitative imaging impossible without new reconstruction algorithms that model photon transport explicitly.

Related work on 225Ac imaging with CZT SPECT (e.g., 2023 EJNMMI Physics) and prompt-gamma timing already highlights the same localization problem. Modified time-of-flight kernels or hybrid Compton-PET systems may eventually recover signal, but standard LAFOV protocols will not.

Future scanner firmware could incorporate 1567 keV coincidence gating; until then, 225Ac dosimetry will continue to rely on surrogate 111In or 68Ga imaging plus population-based kinetics.