Therapeutic Radiopharmaceuticals Targeting Integrin αvβ6

Area of Science:

• Biomedical science
• Radiochemistry
• Oncology

Background:

• Epithelial integrin αvβ6 is overexpressed in many cancers, including pancreatic cancer.
• Integrin αvβ6 is a potential target for targeted radionuclide therapy.

Purpose of the Study:

• To develop and evaluate novel chelator-conjugated peptides targeting integrin αvβ6 for radionuclide therapy.
• To assess the integrin binding affinity, selectivity, and biodistribution of Lu(III) complexes.

Main Methods:

• Synthesis of cyclo(FRGDLAFp(NMe)K) peptide conjugates with DOTPI, DOTAGA, and DOTA chelators.
• Preparation and characterization of Lu(III) complexes.
• In vitro integrin binding assays.
• In vivo biodistribution studies in murine xenografts.

Main Results:

• Lu(III) complexes demonstrated high affinity (0.3–0.8 nM IC50) and selectivity for αvβ6 integrin.
• Biodistribution studies showed comparable results to existing tracers, with potential for theranostics.
• Varying chelator charges influenced hydrophilicity but not significantly biodistribution (except DOTPI).

Conclusions:

• Lu-177 labeled c(FRGDLAFp(NMe)K) derivatives are promising for αvβ6 integrin-targeted radionuclide therapy.
• Combinations with Ga-68 tracers could enable αvβ6 integrin-targeted theranostics.
• Further pharmacokinetic optimization may be needed for clinical success.