Molecular imaging is one of the ten most promising frontiers of medical science in the future. Targeted contrast agents (also known as “molecular probes”) can significantly improve the specificity and sensitivity of molecular imaging. Without targeting contrast agents, is like shooting without bullets, so molecular imaging is the core of molecular imaging techniques.

The advent of multimodal imaging devices facilitates the development of multimodal contrast agents. Theranostic agents have important significance in monitoring the therapeutic effect, so that many diseases are expected to be treated at the molecular level, achieving real targeted therapy. Therefore, the development of multifunctional contrast agents will provide more powerful support for imaging technology and clinical diagnosis.

1. Preclinical studies of ultrasound contrast agents

Novel ultrasound contrast agent with independent intellectual property rights has been successfully developed in our lab, solving the major issues for the clinical translation of the ultrasound contrast agents. We have already got the optimal recipe of the contrast agent and built the standard for large scale production and quality control. The pharmacokinetics, pharmacodynamics, safety and preclinical efficacy studies will be finished soon.

2. Photoacoustic contrast agent

With combined spectral selectivity of laser light and high resolution of ultrasound detection, Photoacoustic (PA) imaging  has proven to be a promising technique for visualizing tissue structures and functions with excellent tissue contrast irrespective to the penetration depth. Employing exogenous contrast agent with high absorption in the NIR region for photoacoustic tomographic (PAT) imaging greatly enhances its molecular sensitivity and functionality.

Due to the inherent features, including outstanding stability, biocompatibility, size controllability and easy surface functionalization for active targeting, both polypyrrole (PPy) and Prusian blue (PB) NPs have received great attention in biomedical application. Particularly, PB is a FDA-approved drug in clinic for safe treatment of radioactive exposure. In our lab, we developed novel PA contrast agents based on PPy and PB NPs, both exhibiting superior absorption efficiency, for enhanced PAT imaging in vitro and in vivo. Most importantly, compared to the conventional imaging techniques, NPs prepared in our lab revealed excellent imaging depth of 4.3 cm, which is nearly 5-folds higher compared to the effective optical penetration depth.

3. MRI/NIR fluorescent dual modal contrast agent

Magnetic resonance imaging (MRI) is the most commonly preferred imaging tool for detecting cancer owing to its excellent soft tissue contrast and unlimited penetration depth. However, the application of MRI is limited by its poor sensitivity. On the contrary, fluorescence imaging with higher sensitivity and real-time imaging is devoid of excellent spatial resolution and penetration depth. To solve this issue, biodegradable superparamagnetic iron oxide (SPIO) nanoparticles (NPs) coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG) and loaded with indocyanine green (ICG) (SPIO@DSPE-PEG/ICG) have been successfully constructed for NIRF/MR dual-modal imaging.  After tail vein injection, the SPIO@DSPE-PEG/ICG NPs were found to selectively accumulate at the tumor site. The increased NIRF signal at tumor regions combined with enhanced T2-weighted MR contrast signals helped to differentiate tumor from the normal cells.

4. Fluorescence/ultrasound dual modal contrast agent

The conundrum of modality selection in clinical diagnostic imaging is that modalities with the highest sensitivity have relatively poor resolution, while those with high resolution have relatively poor sensitivity. For example, fluorescence imaging has enormous potential in the medical and pharmaceutical areas because of high sensitivity but a major problem is poor spatial resolution due to strong scattering. On the contrary, ultrasonic imaging shows high spatial resolution but low sensitivity. To resolve this problem, we have developed novel quantum dot(QD)-modified microbubbles (MBs) in combination of the self-assembly of the gas-filled MBs with layer-by-layer (LbL) deposition of QD nanoparticles onto the resulting MBs.

Through the ultrasound-targeted microbubble destruction, the quantum dots nanoparticles can be released from the microbubbles and enter into cells or tissues for fluorescence imaging. Moreover, combination of ultrasound and microbubble can increase the permeability of tumor tissue, thereby enhancing the accumulation of quantum dots in the tumor. In this way, it is possible to improve the sensitivity of ultrasound imaging and achieve the imaging of extravascular tumor cells. Because layer-by-layer (LbL) self-assembly technology is simple and versatile, quantum dots can be easily replaced by drugs, genes and other different substances, getting a multifunctional composite theranostic drugs. Therefore, it provides a new way of thinking and technology for the development of novel multifunctional contrast agent.