Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Table 1

Imaging studies investigating extracellular vesicles (EVs) biodistribution in vivo.

Imaging technique	EVs labeling	EVs source	Administration route	Biodistribution	Ref
PET	^68Ga and ^64Cu	Breast cancer cells (4T1)	Tail vein and foot pad	Lung, liver, spleen, lymph nodes	[52]
SPECT/CT	Tc	Erythrocytes	Tail vein	Liver and spleen	[53]
	Tc-HMPAO	Macrophages	Tail vein	Liver and spleen	[54]
	^125I	Melanoma cells (B16BL6)	Intravenous injection	Liver, spleen, lungs	[55]
MRI	Paramagnetic cation probes	Melanoma cells (B16-F10)	Food pad	Lymph node	[56]
	Infrared dye	Mouse lymphoma cell line (EL-4)	Intraperitoneal	Kidney, liver, spleen, lungs	[57]
	Near-infrared dye; GFP labeling	Dendritic cells, MSCs from bone marrow	Tail vein, intraperitoneal, subcutaneous	Liver, spleen, gastrointestinal tract, lungs	[58]
	Near-infrared dye	MSCs	Intravenous injection	Kidney in acute kidney injured mice	[59]
	PKH67 dye	Embryonic kidney cells (HEK293T)	Intravenous injection	Tumor targeting	[60]
Optical imaging
	Fluorescent dye and ^111In	Breast cancer cells (4T1)	Tail vein	Liver and spleen	[61]
gLuc-lactadherin						Melanoma cells (B16BL6)	Tail vein	Liver and lungs	[62]
gLuc-lactadherin and PKH67 dye	Melanoma cells (B16BL6)	Tail vein	Macrophages in liver and spleen; endothelial cells in lungs	[63]
gLuc-B and streptavidin-Alexa680	Embryonic kidney cells (HEK293T)	Tail vein	Spleen, liver, lungs, kidney	[64]
Optical imaging and radiolabelling	GFP-tagged CD63	Orthotopically transplanted breast cancer cells	—	Tumor	[65]
Intra vital imaging	Cre-GFP-RFP	Orthotopically transplanted MDA-MB-231	—	Tumor	[66]
	PalmGFP, PalmtdTomato	Mouse lymphoma cell line (EL-4)	Intratumor injection	Tumor	[67]

HMPAO: hexamethylpropyleneamine oxime. gLuc-lactadherin: Gaussia luciferase and a truncated lactadherin reporter. gLuc-B: fusion between a membrane-bound variant of the Gluc reporter and a biotin acceptor peptide.