One radioligand, two targets: covering PSMA-negative prostate tumors that single-target agents miss
- A single DOTA-based construct joins a PSMA-binding EuK motif, an NTSR1-binding neurotensin analogue and an albumin-binding tolyl group, so one molecule can chase two receptors.
- Labeled with gallium-68 for imaging and lutetium-177 for therapy, it bound PSMA-rich cells strongly and NTSR1-expressing cells more modestly, with time-dependent cell uptake and cytotoxicity from the lutetium version.
- The albumin binder extended blood circulation; in mice, PET showed lasting uptake across PSMA-high, intermediate and NTSR1-driven xenografts, and SPECT/CT showed prolonged tumor retention of the lutetium agent.
💡 Points Based on the abstract
A heterobivalent ligand only earns its keep if both pharmacophores stay engaged, and the weaker NTSR1 binding hints that the peptide arm is the one compromising. The linker and albumin-binding tolyl may be crowding the neurotensin pocket. It is also a hefty conjugate to make; a comparison with a mixture of single-target ligands, plus kidney and salivary uptake, would show whether the SAR holds.