4.8 Article

Osteosarcoma-Derived Exosomes as Potential PET Imaging Nanocarriers for Lung Metastasis

Journal

SMALL
Volume 18, Issue 49, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202203999

Keywords

diagnosis; exosomes; lung metastasis; optical imaging; osteosarcoma; positron emission tomography

Funding

  1. Portuguese Foundation for Science and Technology (FCT) [PTDC/BTM-SAL/4451/2020, UIDB/04539/2020, UIDP/04539/2020]
  2. FCT [PD/BDE/150681/2020, BD/06582/2020]

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This study develops an imaging tool using exosomes derived from osteosarcoma cells as natural nanocarriers for the noninvasive detection of lung micrometastasis. The results demonstrate that these exosomes accumulate specifically in metastatic lesions and primary tumors in vivo, showing excellent targeting ability. Optical imaging using exosomes is also able to detect lung metastasis. These findings suggest that tumor-derived exosomes have great potential as targeted imaging agents for the noninvasive detection of small lung metastasis using PET.
Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma-related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected with current clinical tools. Herein, an exosome (EX)-based imaging tool is developed for lung micrometastasis by positron emission tomography (PET) using osteosarcoma-derived EXs as natural nanocarriers of the positron-emitter copper-64 (Cu-64). Exosomes are isolated from metastatic osteosarcoma cells and functionalized with the macrocyclic chelator NODAGA for complexation with Cu-64. Surface functionalization has no effect on the physicochemical properties of EXs, or affinity for donor cells and endows them with favorable pharmacokinetics for in vivo studies. Whole-body PET/magnetic resonance imaging (MRI) images in xenografted models show a specific accumulation of Cu-64-NODAGA-EXs in metastatic lesions as small as 2-3 mm or in a primary tumor, demonstrating the exquisite tropism of EXs for homotypic donor cells. The targetability for lung metastasis is also observed by optical imaging using indocyanine green (ICG)-labeled EXs and D-luciferin-loaded EXs. These findings show that tumor-derived EXs hold great potential as targeted imaging agents for the noninvasive detection of small lung metastasis by PET. This represents a step forward in the biomedical application of EXs in imaging diagnosis with increased translational potential.

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