both
99m Tc-HMPAO of intact exosomes and
99m
Tc-HMPAO released from
degraded exosomes. This should be discriminated.
Considering the trace amount of nanoparticles for imaging used in radionanomedicine, direct radiation toxicity by imaging of radiolabeled exosomes may
not be higher than that of general nuclear medicine imaging procedures in clinics.
Less immunogenicity is anticipated to the self-derived exosomes [61]. Further, the
phospholipid bilayers of exosomes enable direct fusion with the cell membrane of
target tissue, which results in less activation of inflammatory process due to bypass
of the endosomal-lysosomal pathway [67]. Meanwhile, internal radiation dosimetry
assessment is required for clinical translation of radiolabeled exosomes.
Biodistribution of exosomes is mainly dependent on the character of cells of
exosomes origination, which is called homing ability [68]. Due to the complexity
and diversity of the biodistribution of exosomes, imaging with radiolabeled exosomes should be routinely performed as theranostics before the establishment of
therapeutic application.
9.5 Conclusion
The therapeutic potential of exosomes has been increasingly reported in various
clinical applications including regenerative medicine and tumor management. To
reduce toxicity and enhance the efficacy of treatment, specific targeting strategies
using exosomes were developed and regarded as one of the promising biomaterials.
Therefore, validation of specific targeting became very important. For clinical
translation, radionanomedicine is an appropriate method to visualize in vivo distribution of exosomes. The use of theranostic endogenous radionanomedicine using
exosomes will help achieve the goal of the therapeutic use of exosomes sooner in
the clinics.
References
1. S.E. Andaloussi, I. Mäger, X.O. Breakefield, M.J. Wood, Extracellular vesicles: biology and
emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12(5), 347–357 (2013)
2. A.M. Merino, M.J. Hoogduijn, F.E. Borras, M. Franquesa, Therapeutic potential of
extracellular vesicles. Front. Immunol. 5, 658 (2014)
3. H. Choi, D.S. Lee, Illuminating the physiology of extracellular vesicles. Stem Cell Res. Ther.
7(1), 55 (2016)
4. J.L. Hood, R.S. San, S.A. Wickline, Exosomes released by melanoma cells prepare sentinel
lymph nodes for tumor metastasis. Cancer Res. 71(11), 3792–3801 (2011)
5. Ohno S-i, M. Takanashi, K. Sudo, S. Ueda, A. Ishikawa, N. Matsuyama et al., Systemically
injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol.
Ther. 21(1), 185–191 (2013)
178
S. Ha and D. S. Lee
99m Tc-HMPAO of intact exosomes and
99m
Tc-HMPAO released from
degraded exosomes. This should be discriminated.
Considering the trace amount of nanoparticles for imaging used in radionanomedicine, direct radiation toxicity by imaging of radiolabeled exosomes may
not be higher than that of general nuclear medicine imaging procedures in clinics.
Less immunogenicity is anticipated to the self-derived exosomes [61]. Further, the
phospholipid bilayers of exosomes enable direct fusion with the cell membrane of
target tissue, which results in less activation of inflammatory process due to bypass
of the endosomal-lysosomal pathway [67]. Meanwhile, internal radiation dosimetry
assessment is required for clinical translation of radiolabeled exosomes.
Biodistribution of exosomes is mainly dependent on the character of cells of
exosomes origination, which is called homing ability [68]. Due to the complexity
and diversity of the biodistribution of exosomes, imaging with radiolabeled exosomes should be routinely performed as theranostics before the establishment of
therapeutic application.
9.5 Conclusion
The therapeutic potential of exosomes has been increasingly reported in various
clinical applications including regenerative medicine and tumor management. To
reduce toxicity and enhance the efficacy of treatment, specific targeting strategies
using exosomes were developed and regarded as one of the promising biomaterials.
Therefore, validation of specific targeting became very important. For clinical
translation, radionanomedicine is an appropriate method to visualize in vivo distribution of exosomes. The use of theranostic endogenous radionanomedicine using
exosomes will help achieve the goal of the therapeutic use of exosomes sooner in
the clinics.
References
1. S.E. Andaloussi, I. Mäger, X.O. Breakefield, M.J. Wood, Extracellular vesicles: biology and
emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12(5), 347–357 (2013)
2. A.M. Merino, M.J. Hoogduijn, F.E. Borras, M. Franquesa, Therapeutic potential of
extracellular vesicles. Front. Immunol. 5, 658 (2014)
3. H. Choi, D.S. Lee, Illuminating the physiology of extracellular vesicles. Stem Cell Res. Ther.
7(1), 55 (2016)
4. J.L. Hood, R.S. San, S.A. Wickline, Exosomes released by melanoma cells prepare sentinel
lymph nodes for tumor metastasis. Cancer Res. 71(11), 3792–3801 (2011)
5. Ohno S-i, M. Takanashi, K. Sudo, S. Ueda, A. Ishikawa, N. Matsuyama et al., Systemically
injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol.
Ther. 21(1), 185–191 (2013)
178
S. Ha and D. S. Lee