Radiolabeled EXosomes - a nanotheranostic tool for lung micrometastasis in osteosarcoma

Overview

Project Summary

Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma (OS)-related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected with current clinical tools, that progress into lethal lesions during the course of the disease. Therapeutic approaches include the pulmonary metastasectomy, followed by the chemotherapy prescribed to patients with localized disease, which has not led to improvements of survival during the last 30yrs. 

Current imaging modalities demonstrated limited potential in detecting pulmonary metastasis in the early stages, and no risk factors have been reported associated with its initial development. A paradigm shift is needed to overcome this adverse scenario of dismal survival rate in OS, that goes through the early detection of metastatic disease and effective early therapeutic interventions.

Herein, we purpose to develop an exosome-based theranostic nanoplatform for detection and treatment of lung micrometastasis, using tumor-derived exosomes (EXs) as natural delivery vehicles of positron (64Cu) or beta-emitting (177Lu) radionuclides for imaging diagnosis by PET and targeted radionuclide therapy. This proposal takes advantage of the current breakthrough knowledge regarding the crucial role of EXs on the specific metastatic organotropism and from the advances of molecular imaging technology and radionuclide-based therapies, that have been employed with high effectiveness in oncology, paving the way towards individualized medicine.

Main Goals

• Exploit the diagnostic and predictive value of PET image with 64Cu-radiolabelled exosomes data for the risk of lungmetastasis
• Demonstrate the therapeutic efficacy of 177Lu-labelled EXs against lung micrometastasis
• Identify an exosome-based protein signature with added predictive value for the risk of lung metastasis in OS patients

Project Details