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

• First application of a novel approach for labeling peptides to the preparation of Tc-99m and Re-188 with substance-P.
• Characterization of new, structurally identical radioconjugates of substance-P with Tc-99m and Re-188.
• Preliminary biological evaluation of the new Tc-99m and Re-188 peptide radioconjugates.

IntroductionNew 188Re and 99mTc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N]2+ (M=99mTc, 188Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands.MethodsThe new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N]2+ core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas 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]2+ core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives 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.ConclusionNew 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 Re-188 radiopharmaceuticals exhibit identical biological properties.

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