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

Abstract

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 (64Cu). Exosomes are isolated from metastatic osteosarcoma cells and functionalized with the macrocyclic chelator NODAGA for complexation with 64Cu. 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 64Cu‐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.

Disease-microenvironment modulation by bare- or engineered-exosome for rheumatoid arthritis treatment

“…F exosome loaded with D-luciferin using incubation with UV-B. G exosome membrane labeled with ICG-maleimide and NODAGA-maleimide using Michael addition [ 134 ]. Copyright 2022, Wiley …”

“…The exosome-based positron emission tomography (PET) imaging tool for diagnosing lung metastasis was developed by Almedia et al [ 134 ]. The authors used osteosarcoma-derived exosomes for their homing ability, and conjugated the macrocyclic chelator NODAGA using the Michael addition between -SH functional group of exosomal surface and maleimide of NODAGA.…”

Circulating noncoding RNAs: promising biomarkers in liquid biopsy for the diagnosis, prognosis, and therapy of NSCLC

“…An exosome-based imaging tool was developed for the pulmonary metastasis of osteosarcoma by osteosarcoma-derived exosomes as natural nanocarriers. Positron-emitter copper-64 (64 Cu) was utilized to radiolabel OS-derived exosomes, and homologous lung metastatic lesions can be observed by positron emission tomography (PET) [ 190 ]. In future studies, exosomes should receive more attention, and there should be a focus on combining corresponding detection techniques for circulating exosome-derived ncRNAs with specific biological behaviors to further improve the function of ncRNAs as diagnostic and therapeutic biomarkers in NSCLC.…”

Active Targeting Hyaluronan Conjugated Nanoprobe for Magnetic Particle Imaging and Near-Infrared Fluorescence Imaging of Breast Cancer and Lung Metastasis

“…Noninvasive cancer imaging is an emerging field. Various scanning modalities have been utilized for cancer imaging in the lung including computed tomography (CT), positron emission tomography (PET), − magnetic resonance imaging (MRI), , and optical imaging . To better determine the presence of lung metastasis, multimodal imaging has been applied.…”