microPET-Based Biodistribution of Quantum Dots in Living Mice

Abstract

This study evaluates the quantitative biodistribution of commercially available CdSe quantum dots (QD) in mice. Methods: 64 Cu-Labeled 800-or 525-nm emission wavelength QD (21-or 12-nm diameter), with or without 2,000 MW (molecular weight) polyethylene glycol (PEG), were injected intravenously into mice (5.55 MBq/25 pmol QD) and studied using well counting or by serial microPET and region-of-interest analysis. Results: Both methods show rapid uptake by the liver (27.4-38.9 %ID/ g) (%ID/g is percentage injected dose per gram tissue) and spleen (8.0-12.4 %ID/g). Size has no influence on biodistribution within the range tested here. Pegylated QD have slightly slower uptake into liver and spleen (6 vs. 2 min) and show additional low-level bone uptake (6.5-6.9 %ID/g). No evidence of clearance from these organs was observed. Conclusion: Rapid reticuloendothelial system clearance of QD will require modification of QD for optimal utility in imaging living subjects. Formal quantitative biodistribution/imaging studies will be helpful in studying many types of nanoparticles, including quantum dots. Quant um dots (QD) are fluorescent semiconductor nanocrystals with high quantum yield, resistance to photobleaching, narrow emission peak, tunable emission wavelength, and constant excitation profile regardless of emission wavelength, making them interesting for in vivo smallanimal imaging (1,2). Naturally hydrophobic, QD are made water-soluble by surface conjugation (1). Targeting molecules, such as antibodies (3), aptamers (4), peptides (5,6), folate (7), or high-molecular-weight dextran (8) can then be added. Polyethylene glycol (PEG) is commonly attached to the surface of QD for in vivo applications. Pegylation increases in vivo circulation times of nanoparticles and liposomes, likely by sterically hindering the absorption of opsonizing proteins and, thus, delaying recognition and clearance by the reticuloendothelial system (RES) (9,10).QD have been used for in vivo fluorescence imaging for fluorescence sentinel lymph node mapping (11-13), or diffusion analysis of the brain extracellular space (14), in which particle size confines QD to a specific compartment or clearance route. Other studies have used surface modifications to target QD. Akerman et al. used ex vivo fluorescence microscopy to show lung and tumor vasculature targeting of peptide-and 5,000 MW (molecular weight) PEG-coated CdSe/ZnS QD (5). Significant liver and spleen uptake of QD was noted, and it remains unclear whether tumor uptake in this study would have been sufficient for in vivo noninvasive fluorescence imaging. In vivo fluorescence imaging of targets expressed in tumor vasculature and tumor tissues has been reported by our group (a v b 3 integrin targeting using 15-to 20-nm-wide CdSe/ZnS QD coated with RGD peptide and 2,000 MW PEG (6), and others (prostate-specific membrane antigen [PSMA] targeting with 10-to 15-nm-diameter CdSe/ZnS QD coated with anti-PSMA monoclonal antibodies and 5,000 MW PEG (3)). Both reports show significant QD uptake in liver and...

Noninvasive molecular imaging of small living subjects using Raman spectroscopy

“…Biodistribution of these Raman nanoparticles are currently being evaluated in our lab with the use of radiolabels (e.g., with positron emitters) so that quantification of exact nanoparticle concentration can be explored as we have recently done with radiolabeled quantum dots (30). Additional work with tissue targeting of the Raman nanoparticles (SERS and SWNTS) should also help to further expand the eventual utility of the strategies developed in this work.…”

Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles

“…Common examples include fluorescent dyes that are quenched by gold nanoparticles (Dulkeith et al 2002(Dulkeith et al , 2005 or that can be excited by fluorescence resonant energy transfer via a quantum dot serving as donor (Funston et al 2008;Liu et al 2008), for instance for biosensors. Other functions include paramagnetic ligand molecules (Mulder et al 2006a) or chelator molecules for radionuclides (Schipper et al 2007;Shokeen et al 2008).…”

Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

“…Schipper et al 19 studied QD with various coatings after intravenous administration to mice. As seen in other studies, liver was a primary target of uptake, with smaller amounts going to spleen, bone and lung.…”