Self-illuminating 64Cu-doped CdSe/ZnS nanocrystals for in vivo tumor imaging

Abstract

Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide (64)Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The (64)Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of (64)Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of (64)Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection.

Figure 1

Design of self-illuminating ⁶⁴Cu-doped QDs.

Figure 2

(A) PET and optical images of aqueous suspensions of QDs (nonradioactive), free ⁶⁴CuCl₂, mixture of ⁶⁴CuCl₂ and QDs, and ⁶⁴Cu-doped QDs with the same amount of ⁶⁴Cu radioactivity. (B) Comparison of the total photon flux extracted from the phantom images in (A). QDs without excitation light and ⁶⁴Cu presence had virtually no photoluminescence. The total photon flux recorded from the IVIS system without emission filter followed the order of ⁶⁴Cu-doped QDs > ⁶⁴Cu mixed with QDs > ⁶⁴Cu. (C–E) Photon flux obtained from ⁶⁴Cu, mixture of ⁶⁴Cu and QDs, ⁶⁴Cu-doped QDs as well as QDs with QD526 (C), QD580 (D), and QD636 (E) under different emission filters versus the filter wavelengths. Increased photon flux at the emission wavelength of the QDs reflects effective Cerenkov resonance energy transfer (CRET).

Figure 3

(A) Representative whole-body coronal PET images of U87MG tumor-bearing mice at 1, 17, 24, and 42 h after intravenous injection of 250 μCi of ⁶⁴Cu-doped QD580 (n = 3). White arrow, tumor area; black arrow, liver area. Slices for the images are 1 mm thick. QDs show typical reticuloendoethlial system uptake in the liver and spleen as well as tumor accumulation via an EPR effect. (B) ROI analysis of U87MG tumor uptake of ⁶⁴Cu-doped QDs over time (n = 3). (C) Representative whole-body luminescence images of U87MG tumor-bearing mice at 1, 17, 24, and 42 h postinjection of 250 μCi of ⁶⁴Cu-doped QD580 (n = 3). White arrow, tumor area; black arrow, liver area. (D) Comparison of photon flux obtained via an open window without filter and that obtained via a filter covered from 575 to 650 nm in the tumor area 42 h postinjection of 250 μCi of ⁶⁴Cu-doped QDs.