A path toward the clinical translation of nano-based imaging contrast agents.

Recently, nanoparticles have evolved ubiquitously in therapeutic applications to treat a range of diseases. Despite their regular use as therapeutic agents in the clinic, we have yet to see much progress in their clinical translation as diagnostic imaging agents. Several clinical and preclinical studies support their use as imaging contrast agents, but their use in the clinical setting has been limited to off-label imaging procedures (i.e., Feraheme). Since diagnostic imaging has been historically used as an exploratory tool to rule out disease or to screen patients for various cancers, nanoparticle toxicity remains a concern, especially when introducing exogenous contrast agents into a potentially healthy patient population, perhaps rationalizing why several nano-based therapeutic agents have been clinically translated before nano-based imaging agents. Another potential hindrance toward their clinical translation could be their market potential, as most therapeutic drugs have higher earning potential than small-molecule imaging contrast agents. With these considerations in mind, perhaps a clinical path forward for nano-based imaging contrast agents is to help guide/manage therapy. Several studies have demonstrated the ability of nanoparticles to produce more accurate imaging preoperatively, intraoperatively, and postoperatively. These applications illustrate a more reliable method of cancer detection and treatment that can prevent incomplete tumor resection and incorrect assessment of tumor progression following treatment. The aim of this review is to highlight the research that supports the use of nanoparticles in biomedical imaging applications and offer a new perspective to illustrate how nano-based imaging agents have the potential to better inform therapeutic decisions. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

A colorful approach towards developing new nano-based imaging contrast agents for improved cancer detection.

Providing physicians with new imaging agents to help detect cancer with better sensitivity and specificity has the potential to significantly improve patient outcomes. Development of new imaging agents could offer improved early cancer detection during routine screening or help surgeons identify tumor margins for surgical resection. In this study, we evaluate the optical properties of a colorful class of dyes and pigments that humans routinely encounter. The pigments are often used in tattoo inks and the dyes are FDA approved for the coloring of foods, drugs, and cosmetics. We characterized their absorption, fluorescence and Raman scattering properties in the hopes of identifying a new panel of dyes that offer exceptional imaging contrast. We found that some of these coloring agents, coined as "optical inks", exhibit a multitude of useful optical properties, outperforming some of the clinically approved imaging dyes on the market. The best performing optical inks (Green 8 and Orange 16) were further incorporated into liposomal nanoparticles to assess their tumor targeting and optical imaging potential. Mouse xenograft models of colorectal, cervical and lymphoma tumors were used to evaluate the newly developed nano-based imaging contrast agents. After intravenous injection, fluorescence imaging revealed significant localization of the new "optical ink" liposomal nanoparticles in all three tumor models as opposed to their neighboring healthy tissues (p < 0.05). If further developed, these coloring agents could play important roles in the clinical setting. A more sensitive imaging contrast agent could enable earlier cancer detection or help guide surgical resection of tumors, both of which have been shown to significantly improve patient survival.