Evaluating the pharmacokinetics and in vivo cancer targeting capability of Au nanocages by positron emission tomography imaging

Abstract

Gold nanocages have recently emerged as a novel class of photothermal transducers and drug carriers for cancer treatment. However, their pharmacokinetics and tumor targeting capability remain largely unexplored due to the lack of an imaging modality for quick and reliable mapping of their distributions in vivo. Herein, Au nanocages were prepared with controlled physicochemical properties and radiolabeled with (64)Cu in high specific activities for in vivo evaluation using positron emission tomography (PET). Our pharmacokinetic studies with femtomolar administrations suggest that 30 nm nanocages had a greatly improved biodistribution profile than 55 nm nanocages, together with higher blood retention and lower hepatic and splenic uptakes. In a murine EMT-6 breast cancer model, the small cages also showed a significantly higher level of tumor uptake and a greater tumor-to-muscle ratio than the large cages. Quantitative PET imaging confirmed rapid accumulation and retention of Au nanocages inside the tumors. The ability to directly and quickly image the distribution of Au nanocages in vivo allows us to further optimize their physicochemical properties for a range of theranostic applications.

Figure 1

Typical transmission electron microscopy images of DOTA-PEG-AuNCs with an edge length of (a) 54.5±4.4 nm and (b) 30.3±4.2 nm; (c) fast protein liquid chromatography analysis of the 30-nm ⁶⁴Cu-DOTA-PEG-AuNCs; and (d) longitudinal specific activities of the ⁶⁴Cu-DOTA-PEG-AuNCs after incubation at 4 ºC for different periods of time.

Figure 2

Biodistribution of (a) the large ⁶⁴Cu-DOTA-PEG-AuNCs (55 nm) and (b) the small ⁶⁴Cu-DOTA-PEG-AuNCs (30 nm) in C57BL/6 mice (0.37 MBq injection/mouse, n = 4 per group).

Figure 3

Biodistribution of (a) the large ⁶⁴Cu-DOTA-PEG-AuNCs (55 nm) and (b) the small ⁶⁴Cu-DOTA-PEG-AuNCs (30 nm) in EMT-6 tumor bearing mice (0.37 MBq injection/mouse, n = 4 per group).

Figure 4

(a) PET/CT images of the 30-nm ⁶⁴Cu-DOTA-PEG-AuNCs in a mouse bearing an EMT-6 tumor at 1 h, 4 h, and 24 h, respectively, post injection (3.7 MBq injection/mouse). T: tumor, B: bladder. (b) Standardized uptake values (SUV) in tumor and muscle regions obtained from PET/CT images taken at different times. (c) Tumor-to-muscle SUV ratios obtained from PET/CT images taken at different time points.

Figure 5

Tumor autoradiography revealing centralized intratumoral accumulation of the 30-nm ⁶⁴Cu-DOTA-PEG-AuNCs (3.7 MBq injection/mouse) in a mouse bearing an EMT-6 tumor. The tumor was resected at different depth from surface to core region and sectioned into slices of 40 μm thick at 24 h post injection.