In Vivo Cancer Dual-Targeting and Dual-Modality Imaging with Functionalized Quantum Dots

Semiconductor quantum dots (QDs), after surface modification to provide water solubility and biocompatibility, have a promising future in biomedical applications. In this study, a dual receptor-targeting dual-modality PET/near-infrared fluorescence (NIRF) probe was developed for accurate assessment of the pharmacokinetics and tumor-targeting efficacy of QDs.

QDs were modified by β-Glu-RGD-BBN (RGD is arginine-glycine-aspartate acid, and BBN is bombesin) peptides and then labeled with (18)F via the 4-nitrophenyl-2-(18)F-fluoropropionate prosthetic group. Cytotoxicity and cell-binding assay of QD-RGD-BBN were performed with PC-3 cells. In vivo dual-modality PET/NIRF imaging of prostate tumor-bearing mice was investigated using QD-RGD-BBN and 2-(18)F-fluoropropionyl-QD-RGD-BBN ((18)F-FP-QD-RGD-BBN). An in vivo biodistribution study of (18)F-FP-QD-RGD-BBN was performed on normal mice.

QD-RGD-BBN exhibited strong red luminescence (600-800 nm) with the same maximum fluorescence wavelength (705 nm) as QD705 and slightly lower toxicity than that of QD705 in PC-3 cells at concentrations of greater than 30 μg/mL. Uptake of QD-RGD-BBN in PC-3 cells showed no significant decrease in the presence of an excess amount of dimer arginine-glycine-aspartate acid (RGD2) or bombesin(7-14) (BBN) peptide but was blocked significantly in the presence of an excess amount of NH2-RGD-BBN. Dual-function PET/NIRF imaging is able to accurately assess the biodistribution and tumor-targeting efficacy of the (18)F-labeled functionalized QDs.

The functionalized QD probe has great potential as a universal dual-targeting probe for detecting tumors in living subjects, opening up a new strategy for the development of multitargeting multimodality (18)F-labeled QD probes with improved tumor-targeting efficacy.