Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P

Introduction: New 188Re and 99mTc peptide conjugates with substance-P(SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the[M =N]2þ (M=99mTc,188Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. Methods: The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of thetridentate and monodentate ligands to a vial containing a preformed[M=N]2þ core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP,where as the monodentate ligand was a tertiary phosphine.The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re = N]2þ core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small animal YAP(S)PET tomograph. Conclusion: New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high- yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re188 radiopharmaceuticals exhibit identical biological properties.