representative target for targeted therapy. Meanwhile, even though exosomes may
have natural targeting properties, engineering of exosome surface is necessary to
enhance specific delivery of contained anti-tumor drugs to a tumor.
Doxorubin-loaded mouse immature DCs (imDCs) which were engineered to
express an exosomal membrane protein Lamp2b fused to av integrin-specific iRGD
peptide (iRGD-Lamp2b) showed highly efficient targeting and antitumor-effect to
av integrin-positive breast cancer cell lines (MDA-MB-231 and MCF-7) in vitro
and MDA-MB-231 tumor in vivo [59]. The targeted drug-delivery strategies using
exosomes were used not only for cancer therapeutics but also for inflammatory
disease management [60].
9.4 Radionanomedicine for Validation of Therapeutic
Potential of Exosomes
9.4.1 Exosomes and Radionanomedicine
As we have reviewed above, there has been increasing evidence that exosomes have
therapeutic potential as well as pathophysiologic roles in diseases. Most of the
results have been limited in preclinical experiments in vitro and in vivo, and only a
few studies have been conducted in clinical trials [41, 43, 44, 50]. To apply exosomes to the clinical situation as therapeutics successfully, confirmation of specific
targeting of exosomes is mandatory and monitoring of this specific targeting is
critical. To understand the behavior of administered exosomes in vivo,
imaging-based studies are needed. Given the properties of radionuclide imaging
modality and its successful application to clinical nuclear medicine, imaging of
radiolabeled exosomes may be the most promising tracking method to follow the
administered exosomes in human bodies. Radionuclide imaging has characteristics
of non-invasiveness, less toxicity, high penetration, high sensitivity, and easy
quantification. The combination of imaging via radiolabeling and therapeutic
application of exosomes is expected to permit theranostic approaches [61].
9.4.2 Radiolabeling with Various Radioisotopes
Regardless of its potential, only a few studies used radiolabeled exosomes and their
focus was limited mainly on radiolabeling methods and biodistribution in animals.
Radiolabeling with
125 I using streptavidin-biotin system was initially applied for
evaluation of ex vivo biodistribution of intravenously administered B16BL6 murine
melanoma cell-derived exosomes in mice, which needed genetic modification of
B16BL6 cells to produce streptavidin [12]. Radiolabeling with
131 I of 4775-LuT
breast cancer cell-derived exosomes was also reported [62]. In addition, direct
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have natural targeting properties, engineering of exosome surface is necessary to
enhance specific delivery of contained anti-tumor drugs to a tumor.
Doxorubin-loaded mouse immature DCs (imDCs) which were engineered to
express an exosomal membrane protein Lamp2b fused to av integrin-specific iRGD
peptide (iRGD-Lamp2b) showed highly efficient targeting and antitumor-effect to
av integrin-positive breast cancer cell lines (MDA-MB-231 and MCF-7) in vitro
and MDA-MB-231 tumor in vivo [59]. The targeted drug-delivery strategies using
exosomes were used not only for cancer therapeutics but also for inflammatory
disease management [60].
9.4 Radionanomedicine for Validation of Therapeutic
Potential of Exosomes
9.4.1 Exosomes and Radionanomedicine
As we have reviewed above, there has been increasing evidence that exosomes have
therapeutic potential as well as pathophysiologic roles in diseases. Most of the
results have been limited in preclinical experiments in vitro and in vivo, and only a
few studies have been conducted in clinical trials [41, 43, 44, 50]. To apply exosomes to the clinical situation as therapeutics successfully, confirmation of specific
targeting of exosomes is mandatory and monitoring of this specific targeting is
critical. To understand the behavior of administered exosomes in vivo,
imaging-based studies are needed. Given the properties of radionuclide imaging
modality and its successful application to clinical nuclear medicine, imaging of
radiolabeled exosomes may be the most promising tracking method to follow the
administered exosomes in human bodies. Radionuclide imaging has characteristics
of non-invasiveness, less toxicity, high penetration, high sensitivity, and easy
quantification. The combination of imaging via radiolabeling and therapeutic
application of exosomes is expected to permit theranostic approaches [61].
9.4.2 Radiolabeling with Various Radioisotopes
Regardless of its potential, only a few studies used radiolabeled exosomes and their
focus was limited mainly on radiolabeling methods and biodistribution in animals.
Radiolabeling with
125 I using streptavidin-biotin system was initially applied for
evaluation of ex vivo biodistribution of intravenously administered B16BL6 murine
melanoma cell-derived exosomes in mice, which needed genetic modification of
B16BL6 cells to produce streptavidin [12]. Radiolabeling with
131 I of 4775-LuT
breast cancer cell-derived exosomes was also reported [62]. In addition, direct
176
S. Ha and D. S. Lee