Dual-labeling strategies for nuclear and fluorescence molecular imaging: a review and analysis

Abstract

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging.

Fig. 1

Number of PubMed publications per year describing clinical NIRF studies (as of July 2011).

Fig. 2

a Schematic representing the physics of nuclear imaging modalities whereby upon radiative decay, high-energy photons are emitted and detected with limited scattering effects. b Schematic representing the physics of NIRF imaging whereby upon activation of the fluorophore by excitation light, the emitted fluorescence signal is highly scattered in tissue prior to detection by a CCD-based camera system.

Fig. 3

Examples of BFCAs used for radiolabeling (MW shown).

Fig. 4

Experimental design for characterization of NIRF dyes in water, buffers, and radioactive solutions.

Fig. 5

Relative brightness of various NIRF dyes in water. Samples were normalized with ICG (φ = 0.016) at 785 nm excitation and 830 nm emission as a standard.

Fig. 6

Relative brightness of various NIRF dyes in buffers. Samples were normalized with ICG (φ = 0.016) at 785 nm excitation and 830 nm emission as a standard.

Fig. 7

Relative brightness of various NIRF dyes in radioactive solutions of ⁶⁴Cu (11.1 MBq) and ⁶⁸Ga. Three different activity levels of ⁶⁸Ga were used: low = 22.2 MBq, med = 59 MBq, high = 152 MBq. Samples were normalized with ICG (φϕ = 0.016) at 785 nm excitation and 830 nm emission as a standard.