An Integrated Quad-Modality Molecular Imaging System for Small Animals

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-F-18-FDG, [Tc-99m(HYNIC-3PRGD(2))(tricine)TPPTS)] (Tc-99m-3PRG(2)) (HYNIC = 6-hydrazinonicotinyl; TPPTS = trisodium triphenylphosphine-3,3',3 ''-trisulfonate; 3PRGD(2) = PEG(4)-E[PEG(4)-c (RGDfK)](2)), and 3-(triethoxysilyl) propyl-Cy7-entrapped core-crosslinked 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.