Diagnostic Twins: Exploring the Radiohybrid Concept with Iodine-123 and Lanthanum-133 for PSMA-Targeted SPECT and PET Imaging

PSMA-targeted ligands
containing macropa as highly effective chelators
for 225Ac were developed for endoradiotherapy, alongside
complementary diagnostic approaches using 133La for PET
and 123I for SPECT within the radiohybrid concept. These
ligands include mono- and bivalent PSMA-targeting structures with
optional albumin-binding moieties, enabling both early- and late-stage
imaging while maintaining identical pharmacological behavior. Radiolabeling
was performed at the macropa side with 133La and at the
albumin-binding side with 123I. All ligands showed high
PSMA affinity (Ki = 2.3–9.4 nM)
and remarkable internalization rates up to 97% in vitro. In vivo studies
using LNCaP tumor-bearing mice demonstrated comparable tumor uptake
across all conjugates, regardless of the radionuclide. Advantageously,
quantitative PET and SPECT blood measurements correlated closely with
ex vivo data and metabolite analysis, additionally confirming the
high in vivo stability with minimal deiodination during renal excretion
and highlighting the suitability for dosimetric applications.