Noninvasive Gastrointestinal Tract Imaging Using BSA-Ag2Te Quantum Dots as a CT/NIR-II Fluorescence Dual-Modal Imaging Probe in Vivo.

The combination of high-resolution computed tomography (CT) and the real-time sensitive second near-infrared window (NIR-II) fluorescence bioimaging can provide complementary information for the diagnosis, progression and prognosis of gastrointestinal disorders. Ag2Te quantum dots (QDs) are a kind of promising CT/NIR-II fluorescence dual-modal imaging probe due to their high atomic number and narrow bandgap. However, conventional Ag2Te QDs synthesized by oil phase approaches often suffer from complicated steps, harsh reaction conditions, and toxic organic solvents. Herein, we report the synthesis of bovine serum albumin (BSA)-Ag2Te QDs using a biomineralization approach for CT/NIR-II fluorescence dual-modal imaging of the gastrointestinal tract. The BSA-Ag2Te QDs are fabricated in a facile one-pot approach under mild conditions and exhibit homogeneous size, favorable monodispersity, admirable aqueous solubility, excellent X-ray attenuation properties, and outstanding NIR-II fluorescence performance. In vivo imaging experiments show that BSA-Ag2Te QDs can be used in gastrointestinal tract CT/NIR-II dual-modal imaging with high spatiotemporal resolution and sensitivity. In addition, in an intestinal obstruction mouse model, accurate lesion positioning and imaging-guided obstruction relief surgery are successfully realized based on BSA-Ag2Te QDs. Besides, BSA-Ag2Te QDs have outstanding biocompatibility in vitro and in vivo. This study presents a high-performance and biosafe CT/NIR-II fluorescence dual-modal imaging probe for visualizing the gastrointestinal tract in vivo.

Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

IR820, an analog of FDA-approved indocyanine green, is a promising second near-infrared window (NIR-II) fluorescence probe with better NIR-II fluorescence stability and great clinical transformation potential. Moreover, its fluorescence can be further remarkably enhanced by the interaction with albumin. Therefore, it is significant to flexibly design IR820-albumin complex using endogenous or exogenetic albumin to meet the requirements of different biological applications. Herein, we show the rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction. We compared the NIR-II fluorescence imaging ability of IR820 pre-incubated with albumin or not to visualize tumors and the gastrointestinal tract in vivo and found that the formation of IR820-albumin was essential for the intense NIR-II fluorescence. For imaging-guided tumor treatment, after intravenous injection of free IR820, IR820-albumin complex can be formed in vivo due to the presence of plenty of albumin in the blood. For imaging-guided gastrointestinal obstruction removal, IR820-albumin complex should be synthesized in vitro before oral administration. NIR-II fluorescence imaging-guided surgeries were successfully realized in both tumor resection and gastrointestinal obstruction removal. Besides, toxicity assessments in vitro and in vivo confirmed the good biocompatibility of IR820. Our study provides a flexible paradigm for IR820-based NIR-II fluorescence imaging and surgical navigation towards different diseases.

Gram-scale synthesis of a neodymium chelate as a spectral CT and second near-infrared window imaging agent for visualizing the gastrointestinal tract in vivo.

The diagnosis of gastrointestinal (GI) tract diseases is frequently performed in the clinic, so it is crucial to develop high-performance contrast agents for real-time and non-invasive imaging examination of the GI tract. Herein, we show a novel method to synthesize a neodymium (Nd) chelate, Nd-diethylenetriaminepentaacetic acid (Nd-DTPA), on a large scale without byproducts for spectral computed tomography (CT) and second near-infrared window imaging of the GI tract in vivo. The Nd-DTPA was simply generated by heating the mixture of Nd2O3 and DTPA in water at 85 °C for 2 h. This dual-modal imaging agent has the advantages of a simple and green synthesis route, no need of purification process, high yield (86.24%), large-scale production capability (>10 g in lab synthesis), good chemical stability and excellent water solubility (≈2 g mL-1). Moreover, the Nd-DTPA emitted strong near-infrared fluorescence at 1308 nm, and exhibited superior X-ray attenuation ability compared to clinical iohexol. The proposed Nd-DTPA can integrate the complementary merits of dual-modal imaging to realize spatial-temporal and highly sensitive imaging of the GI tract in vivo, and accurate diagnosis of the location of intestinal obstruction and monitor its recovery after surgery. The developed highly efficient method for the gram-scale synthesis of Nd-DTPA and the proposed spectral CT and second near-infrared window dual-modal imaging strategy provide a promising route for accurate visualization of the GI tract in vivo.

An integrated quad-modality molecular imaging system for small animals.

UNLABELLED: We developed a novel integrated quad-modality system that included 3 molecular imaging methods (PET, SPECT, and fluorescence molecular imaging [FMI]) and 1 anatomic imaging modality (CT). This system could study various biologic processes in the same animal using multiple molecular tracers. In addition to the technology development, we also discussed the optimization strategy of the imaging protocols. The performance of this system was tested, and the in vivo animal experiment showed its power to trace 3 different molecular probes in living tissues. Our results demonstrated that this system has a great potential for the preclinical study of diseases. METHODS: A prototype system integrating PET, SPECT, CT, and a charge-coupled device-based free-space FMI system has been developed. Imaging and fusion capabilities of the system were evaluated by a multimodality phantom. In addition, a mouse disease model with both tumor and inflammation was studied by this system to examine the in vivo performance. The 3 types of molecular probes-(18)F-FDG, [(99m)Tc(HYNIC-3PRGD2)(tricine)(TPPTS)] ((99m)Tc-3PRG2) (HYNIC = 6-hydrazinonicotinyl; TPPTS = trisodium triphenylphosphine-3,3',3″-trisulfonate; 3PRGD2 = PEG4-E[PEG4-c(RGDfK)]2), and 3-(triethoxysilyl) propyl-Cy7-entrapped core-cross-linked polymeric micelle (Cy7-entrapped CCPM) nanoparticles-were used to target 3 different biologic processes in the tumor caused by pulmonary adenocarcinoma A549 cells. Moreover, the strategy to optimize multimodal molecular imaging procedure was studied as well, which could significantly reduce the total imaging time. RESULTS: The imaging performance has been validated by both phantom and in vivo animal experiments. With this system and optimized imaging protocol, we successfully differentiated diseases that cannot be distinguished by a single molecular imaging modality. CONCLUSION: We developed a novel quad-modality molecular imaging system that integrated PET, SPECT, FMI, and CT imaging methods to obtain whole-body multimodality images of small animals. The imaging results demonstrated that this system provides more comprehensive information for preclinical biomedical research. With optimized imaging protocols, as well as novel molecular tracers, this quad-modality system can help in the study of the physiology mechanism at an unprecedented level.