Radiolabeled Exosomes for the Early Detection of Metastases and to Predict Breast Cancer Premetastatic Niche

Abstract : Since current diagnostic tools fail to detect breast cancer (BC) metastatic spread at a very early stage, we proposed a new approach for the early detection of metastatic disease in BC patients using cancer cell derived particles known as exosomes as a guide. We hypothesized that exosomes tagged with appropriate radionuclides could be used as molecular imaging probes to study and non-invasively image metastatic spread, and to detect pre-metastatic niches using single-photon emission computed tomography (SPECT) or Positron emission tomography (PET). During this report period we have: 1) isolated and characterized exosomes from a series of BC cell lines of different metastatic capacity and tropism, 2) radiolabeled isolated BC exosomes with different radionuclides, such as 111In, 64Cu, 89Zr . We plan to 3) study the uptake and subsequent intracellular transport of radiolabeled exosomes by different cell types involved in premetastatic niche formation, 4) to study the in vivo stability, pharmacokinetics and biodistribution of radiolabeled exosomes following intravenous administration in naive and pathological mouse models. 5) Study the biodistribution and tumor uptake of radiolabeled exosomes (derived from peripheral blood of BC patients) in BC.