Design considerations for targeted optical contrast agents

Abstract

Optical fluorescence imaging with the right combination of imaging modality and targeted contrast agents offers tremendous improvement in intraoperative imaging and clinical output (i.e., image-guided cancer surgery). Therefore, it is of paramount importance to gain an in-depth knowledge in the design of targeted contrast agents to meet clinical requirements. Currently, there are several clinically approved contrast agents available; however, none perform optimally in vivo by providing optimum sensitivity, stability, specificity, and safety for target imaging, diagnosis, and therapy. In this review, we discuss basic design considerations for targeted contrast agents in terms of optical and physicochemical properties, biological and physiological interactions, and biodistribution and targeting.

Keywords: Near-infrared imaging; biodistribution; optical imaging; targeted contrast agent.

Figure 1

Relative sizes of contrast agents: HD ranges for contrast agents useful for biomedical imaging (top row) and naturally occurring materials (bottom row). ICG = indocyanine green. The threshold between rapid renal clearance and hepatobiliary clearance is about 5.5 nm in HD. EPR (enhanced permeation and retention) is efficient when the size of an injected molecule is between 10 nm and 200 nm in HD. [Modified from Ref (12); Copyright permission from Decker Publishing]

Figure 2

Pharmacokinetics: the plasma half-life is composed of distribution phase (t_1/2,α) and elimination phase (t_1/2,β) as indicated in purple and blue colors, respectively. Shown are blood half-life examples obtained from ZW800-1 (28) (a small molecule, 1 nm in HD), QD-Cys (25) (a small nanoparticle, 5 nm in HD), and QD-PEG (26) (a typical-sized nanoparticle, 8 nm in HD)

Figure 3

In vivo NIR fluorescence imaging of nanoparticles in Sprague-Dawley rats. 20 pmol/g of PEGylated InAs(ZnS) quantum dots were injected intravenously 4 h prior to imaging. Abbreviations used are: DHLA, dihydrolipoic acid; PEG, polyethylene glycol; Ki, kidneys; Bl, bladder; Li, liver; Pa, pancreas; Sp, spleen; and In, intestine. λ_Exc=667±11 nm; λ_Em=720 nm long pass. NIR fluorescence images have identical exposure times and normalizations. Scale bars =500 µm. [Adapted from Ref (26); Copyright permission from ACS Publications]