Radiolabeled exosomes for theranostics: Personalized tailored therapy through imaging

Figure 1 Schematic representation of direct radiolabeling strategies for exosomes. Exosomes released from cells contain several biological materials, such as proteins, lipids, and nucleic acids, which can be utilized as binding or entry sites for radiolabels. Intraluminal labeling employs ionophores that facilitate passive diffusion across the lipid bilayer, allowing intercellular binding to biomolecules. Lipophilic radiotracers are converted into hydrophilic forms intraluminally, resulting in their entrapment within the vesicle lumen. Surface labeling utilizes bifunctional chelators, such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid or 1,4,7-triazacyclononane-1,4,7-triacetic acid, which coordinate redox reactions with membrane phospholipids. These radiolabeled exosomes enable noninvasive in vivo tracking through positron emission tomography or single-photon emission computed tomography imaging. HMPAO: Hexamethylpropyleneamine oxime; NHS: N-hydroxysuccinimide; NOTA: 1,4,7-triazacyclononane-1,4,7-triacetic acid; DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; SPECT: Single-photon emission computed tomography; CT: Computed tomography; PET: Positron emission tomography. Created in BioRender, https://BioRender.com/uoiu87p.

Figure 2 Schematic representation of indirect radiolabeling strategies. Exosomes released from cells contain several biological materials, such as proteins, lipids, and nucleic acids, which can be utilized as binding or entry sites for radiolabels. Indirect labeling incorporates radiotracers into exosomes through chelation, electrostatic binding, lipid insertion, or carrier-mediated (bio-orthogonal) methods, enabling stable, noninvasive positron emission tomography/single-photon emission computed tomography imaging tracking without compromising vesicle integrity. Created in BioRender, https://BioRender.com/278r8w1. Science Suite Inc. dba BioRender (“BioRender”) has granted Prakash Gangadaran permission to use this Completed Graphic in accordance with BioRender’s Terms of Service and Academic License Terms (“License Terms”).