A ⁶⁴ Cu-porphyrin-based dual-modal molecular probe with integrin α_v β₃ targeting function for tumour imaging

Pyropheophorbide-a (Pyro) is a promising multifunctional molecule for multimodal tumour imaging and photodynamic therapy, but its clinical applications are seriously restricted by the limited tumour accumulation capability. Here, we designed and synthesized a small-molecule probe that achieved specific dual-modal tumour imaging based on Pyro. Briefly, a novel molecule combining Pyro, an RGD dimer peptide (3PRGD₂ ) and ⁶⁴ Cu, was designed and synthesized, and the obtained molecule, ⁶⁴ Cu-Pyro-3PRGD₂ , exhibited high tumour specificity in both positron emission tomography and optical imaging in vivo. c (RGDfk) peptide blocking significantly reduced the efficacy of the probe, which confirmed the integrin α_V β₃ targeting of this molecular probe. ⁶⁴ Cu-Pyro-3PRGD₂ had very low accumulation in normal organs and could be rapidly cleared through kidney metabolism, which prevented the potential damage to adjacent normal tissues. Overall, combining tumour targeting, dual-modal imaging, and biosafety, ⁶⁴ Cu-Pyro-3PRGD₂ has the potential for clinical use as a molecular imaging probe for tumour diagnosis.