Metastases of tumors are associated with more than 90% of cancer deaths. Despite years of therapeutic development, mortality has improved only incrementally by few months at best. The preclinical development phase for modern metastatics currently misses critical quantitative information on metastatic progression. Multi-point in vivo observation of early metastasis and quantitative assessment of its development would enable unprecedented precision of longitudinal control. PhotoSound Technologies, Inc. proposes a novel platform for in vivo molecular imaging that addresses the critical barrier in quantitative preclinical imaging of metastasis via contrasted dual-modality 3D imaging approach. The proposed project promises to enable in vivo quantification of numbers and volumes of early metastatic tumors, which is critical for preclinical development of future anti-metastatics. The platform integrates a 3D photoacoustic tomography into a multi-modality imaging platform with a coregistered 3D fluorescence unit (PAFT) and a switchable optical nanoprobe targeted to the studied metastatic cells. The nanoprobe has capability to activate optical and fluorescence contrasts upon external illumination with safe levels of pulsed laser radiation, and it was designed to maximize benefits of dual-modality PAFT imaging. The fluorescence imaging component of PAFT is used to boost detection sensitivity by providing low-resolution spatial constraint for the distribution of activated nanoprobes, which are then precisely mapped in 3D by photoacoustic imaging component. The ultimate objective is to maintain the molecular sensitivity of state-of-the-art fluorescence techniques, while boosting spatial resolution of the detected metastasis 10-fold. Current trends on $1.5B market of in vivo small animal imaging favor commercial introduction of the proposed multi-modal imaging platform, which is designed for table-top application and has a 3D anatomical reference component implemented through a photoacoustic unit. PAFT could be also used as a universal instrument for 3D functional imaging of volumetric blood content and oxygenation without a need for any contrast agent, imaging of various NIR absorbing probes and bioluminescent cells. Such versatility would be attractive for Animal Research Facilities engaged in a broad spectrum of fundamental and preclinical imaging studies. Phase I project will demonstrate feasibility for the PAFT-nanoprobe imaging platform to detect and quantify early metastasis in a preclinical murine model. The focus of Phase II will be the development of a commercial imaging platform that is optimized to monitor the in vivo effects of anti-metastatic therapies. When our system is benchmarked against the current standards of optical imaging, we expect to find a 10x increase in spatial resolution enabling detection of metastases separated by only 0.5 mm, as well as quantitative assessment of individual tumor volumes.
More than 90% of cancer deaths occur after the initiation of metastasis prioritizing the development of new anti-metastatic therapies. Small animal models of human cancer represent the golden standard and the first step in preclinical development phase of all promising anti-metastatics. High-throughput screening of such models requires non-invasive imaging techniques, which are currently incapable of detection, quantification, and monitoring response of early metastatic lesions. This project proposes development of a novel small animal imaging platform integrating photoacoustic tomography and fluorescence in a single compact instrument, enabling high-resolution 3D rendering and anatomical registration of metastatic lesions. Adequate sensitivity and specificity is provided by an optically switchable dual contrast nanoprobe with cancer-specific molecular targeting. The developed technology will be commercially available for preclinical and research applications in the area of cancer. 1
