Conclusion
Conjugation of our novel add-on molecule, NMEB or DMEB, to potential tracers or therapeutic agents improved blood half-life and tumor uptake and could transform such agents into theranostic entities.
Methods
The truncated Evans blue molecule was conjugated with the chelator NOTA or DOTA, and the resulting conjugate was denoted as NMEB or DMEB, respectively. As a proof of concept, we coupled NMEB and DMEB to c(RGDfK), which is a small cyclic arginine-glycine-aspartic acid (RGD) peptide, for targeting integrin αvβ3 NMEB and DMEB were radiolabeled with 64Cu and 90Y, respectively, and tested in xenograft models.
Results
The resulting radiolabeled conjugates showed a prolonged circulation half-life and enhanced tumor accumulation in integrin αvβ3-expressing tumors. Tumor uptake was markedly improved over that with NOTA- or DOTA-conjugated c(RGDfK). Tumor radiotherapy experiments in mice with 90Y-DMEB-RGD showed promising results; existing tumors were eliminated.