^86/90Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics

Area of Science:

• Nuclear medicine
• Oncology
• Bioconjugation chemistry

Background:

• Pancreatic cancer (PaCa) is aggressive with poor prognosis due to late diagnosis and limited therapies.
• Tissue factor (TF) overexpression correlates with tumor progression in pancreatic cancer.
• A multifunctional theranostic system is crucial for effective PaCa management.

Purpose of the Study:

• To develop and evaluate a novel theranostic agent for pancreatic cancer targeting tissue factor (TF).
• To utilize the 86Y/90Y radioisotope pair for combined PET imaging and radionuclide therapy.
• To assess the efficacy of the TF-targeted theranostic agent in preclinical models.

Main Methods:

• Conjugation of a TF-targeted monoclonal antibody (ALT836) with the 86Y/90Y pair via DTPA.
• Serial PET imaging of 86Y-DTPA-ALT836 in pancreatic cancer xenografts to assess biodistribution.
• Therapeutic evaluation using 90Y-DTPA-ALT836 and monitoring tumor burden via Cherenkov luminescence imaging.

Main Results:

• High uptake and retention of 86Y-DTPA-ALT836 in pancreatic tumors, confirmed by PET and ex vivo studies.
• Significant tumor growth inhibition and tumor damage observed with 90Y-DTPA-ALT836 therapy.
• Cherenkov luminescence imaging effectively monitored therapeutic response and tumor burden.

Conclusions:

• The 86Y/90Y theranostic pair provides excellent PET imaging contrast for TF-expressing pancreatic tumors.
• TF-targeted radioimmunotherapy with 90Y-DTPA-ALT836 demonstrates promising therapeutic outcomes.
• This theranostic approach offers a potential strategy for improved pancreatic cancer management.