# Molecular Imaging with \({}^{68}\)Ga Radio-Nanomaterials: Shedding Light on Nanoparticles
## 4 Biomedical Applications of \({}^{68}\)Ga-Labeled Nanoparticles
### Other Nanoparticles  
Besides the above mentioned nanoprobes, many other nanoparticle types have been developed for MI. Examples of these include Au nanoparticles [149; 150], dendrimers [151; 152], carbon nanotubes [153; 154], or silica nanoparticles [155; 156]. Figure 8: Fluorescence emission spectrum for UCNPs doped with several lanthanides after excitation with CW laser at 980 nm [139]. Multiple emission peaks can be observed at 360 nm, 451 nm, 476 nm and 800 nm. [PERSON] et al. [157] developed glucose-coated gold nanoparticles radiolabeled with \({}^{68}\)Ga via NOTA ligand, functionalized with opioid-related peptides to improve BBB crossing. NOTA was functionalized with linkers containing a thiol-ending group to attach the chelator to the gold surface. \({}^{68}\)Ga incorporation efficiencies obtained range from 85 to 94% within 30 min and 70 \({}^{\circ}\)C. In vivo PET imaging and ex vivo quantification in rats revealed different biodistribution patterns that depend on peptides with which nanoparticles were functionalized. Only nanoparticles functionalized with Leu-enkephalin peptide revealed improved brain accumulation. [PERSON] et al. [108] took advantage of the EPR effect in cancerous tissue vasculature to visualize [PERSON]'s ascites tumors in Balb/c mice. They radiolabeled generation four polyamido-amine dendrimers (G4-PAMAM-D) with \({}^{68}\)Ga via DOTA-NHS chelator, achieving more than 93% radiolabeling efficiency. Dendrimer-based nanoprobe remained stable in serum at room temperature up to 4 h. Passive probe accumulation at tumor site was confirmed using PET imaging. [PERSON] et al. [158] synthesized a nanoradiotracer composed by a polysiloxane matrix scaffold surrounded by DOTAGA[Gd\({}^{3+}\)] and NODAGA[\({}^{68}\)Ga\({}^{3+}\)] for PET/MRI. NODAGA and DOTAGA were grafted onto the NP shells by amide bond formation between activated NHS groups of NODAGA and anhydride function of DOTAGA and the amino groups in shell. Nanoparticles were successfully radiolabeled with a high radiochemical purity (>97%) and were stable up to 3 h. They injected them in vivo in Swiss mice and observed fast renal clearance after retro-orbital injection. [PERSON] et al. [107] made use of this same nanoradiotracer to prove its successful passive accumulation in mouse xenograft tumor models of U87 MG human glioblastoma, via PET and MRI imaging, thus demonstrating its usefulness as a cancer imaging agent. Serum metabolite assessment in urine, serum and tumor samples proved nanoprobe remained unmetabolized up to 60 min post-injection. [PERSON] et al. [159] prepared \({}^{68}\)Ga-labeled porous zirconia nanoparticles using DOTA as chelating ligand. DOTA was adsorbed on the surface of zirconia nanoparticles. Radiolabeling showed high efficiency (90.5-97.5%) and they were stable in HEPES and human blood serum. They tested biodistribution in vivo in mice. PET imaging after intravenous probe injection revealed major liver and spleen nanoradiotracer accumulation. [PERSON] et al. [160] radiolabeled silica nanoparticles with several radiometals using a chelator free approach, incorporating cations in the pores of the nanoparticles. \({}^{68}\)Ga was successfully incorporated to the nanoparticles with 99% radiolabeling yield. They assessed nanoprobe biodistribution in vivo in athymic nude mice and compared it to the biodistribution of free \({}^{68}\)Ga. PET images acquired 1 and 3 h post injection reveal nanoprobe mainly accumulates in liver and spleen, whereas free gallium presented an entirely different biodistribution profile, with the bladder as major organ eliminating free \({}^{68}\)Ga.  
[PERSON] et al. [161] labeled poly2,3-epoxypropylmethacrylate (EPMA) latex nanoparticles in a chelator-free manner with Gd\({}^{3+}\) for MRI, \({}^{111}\)In for gamma scintigraphy or \({}^{68}\)Ga for PET imaging. \({}^{68}\)Ga nanoradiotracer was obtained with 0.2 MBq/mg nanoparticles. It was posteriorly injected in Wistar rats to assess biodistribution using PET imaging.