# Molecular Imaging with \({}^{68}\)Ga Radio-Nanomaterials: Shedding Light on Nanoparticles
## 4 Biomedical Applications of \({}^{68}\)Ga-Labeled Nanoparticles
### Liposomes  
Liposomes are probably the most used nanomaterial in nanomedicine for research and clinical applications. Liposomes are spherical vesicles consisting on amphiphilic phospholipids (e.g., phosphatidylcholine, phosphatidylcholine-ethanolamine, phosphatidylserine and phosphatidylcholine-glycerol) that form a lipid bilayer enclosing an aqueous core. This structure allows the encapsulation of both hydrophobic and hydrophilic molecules, which provide diverse and tunable properties to the nanoplatform.  
Primarily, liposomes have been studied as drug delivery agents [111; 112; 113; 114]; nevertheless, increased attention has been brought to the development of multifunctional liposomes as theranostic agents. With this kind of platforms, diagnosis and treatment can be achieved simultaneously. For this purpose, liposomes are either labeled or loaded with both, the therapeutic agent and the imaging probe. Visualization of liposomes with T\({}_{1}\)-weighted MRI [115; 116] and T\({}_{2}\)-weighted MRI [117], PET [118; 119; 120] and OI [121], among others, has been achieved in several studies.  
[PERSON] et al. [122] compared radiolabeling PEGylated-DTPA liposomes using different radiometals: \({}^{111}\)In, \({}^{999}\)Tc for SPECT; \({}^{68}\)Ga for PET and \({}^{177}\)Lu for therapeutic applications. DTPA served as chelate ligand on the surface of the liposomes. \({}^{68}\)Ga radiolabeling of these nanoparticles was achieved with 98% radiochemical yield. In vivo fate of this nanoradiotracer was evaluated in Lewis rats, showing modest blood circulation time. Fused PET/MR images acquired 20 min revealed major liver and spleen accumulation. [PERSON] et al. [119] synthesized DSPE-PEGylated liposomes loaded with maghemite nanoparticles in their lumen in order to perform magnetic targeting and use them as MRI contrast agents. They incorporated glucose in the lipid formulation as an extra tumor-targeting moiety. Liposomes were radiolabeled with \({}^{68}\)Ga using NODAGA as chelating agent; obtaining low radiolabeling yields (10%) at room temperature, but reaching 70% radiolabeling yield at 80 \({}^{\circ}\)C. These nanoradiotracers were injected through the retro-orbital sinus of U87 MG tumor-bearing mice. They compared probe accumulation in the tumors with and without the use of magnetic targeting; and with and without glucose moiety in the liposome formulation. PET images acquired 30 min post-injection reveal increased nanoradiotracer accumulation in those with magnetic targeting. Effect of glucose targeting showed contradictory results, as MRI showed positive results that resulted non-significant with PET and ex vivo quantification (Figure 7).  
Figure 6: (**a**) PET/CT imaging of a mouse with LPS-induced lung inflammation 1 h post i.v. injection of \({}^{68}\)Ga nanoradiotracer functionalized with N-cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF). Neutrophil recruitment in the lungs is clearly observed. (**b**) PET/CT image of a neutrophil-depleted, LPS-treated mouse 1 h post i.v. injection of \({}^{68}\)Ga nanoradiotracer functionalized with cFLFLF. Adapted from [PERSON] et al. [73].