Optical imaging for Translational Cancer Research

描述（由申请人提供）：在基础和转化生物医学研究中，使用PET、SPECT、CT、光学、超声和MRI等模式对小动物进行成像的重要性无论如何强调都不过分。对小动物成像而不牺牲它们的能力允许研究者a）验证用于诊断的新型探针，B）进行体内药代动力学研究，c）评估用于预防和治疗的研究性生物分子，以及d）确定治疗的有效性。小动物成像减少了研究和控制成本所需的动物数量，同时提供了科学有效和统计学显著的数据。在托马斯杰斐逊大学（TJU），有300多名基础和医生科学家从事肿瘤学，神经病学和心脏病学的生物医学研究。四年前，TJU建立了一个小动物成像设施，由PI在放射科指导。该设施包括CT、PET/SPECT和PET扫描仪。迄今为止，已有33名调查人员使用了这一设施，并在同行评审的期刊上发表了30多篇文章。在纵向研究中，动物接受不同水平和频率的辐射剂量。人们对这种辐射的未知后果表示担忧，特别是在治疗干预，血管生成抑制和成像细胞凋亡的有效性等研究中。同时，研究人员认识到，在光学成像中，由于其在体内的深度而损害病变可视化的任何荧光染料都可以被放射性标记用于PET或SPECT成像。造影和光学成像的作用是互补的，我们将协同使用这两种方式。例如，我们实验室开发的一种成功的PNA构建体，当用Cu-64标记时，能够对异种移植物中的kRAS癌基因mRNA进行PET成像，该构建体已经用近红外（NIR）染料NIR 664标记，用于对小鼠中的人结肠直肠癌异种移植物进行成功的光学成像。同样，我们实验室开发的用于人乳腺癌成像的Cu-64标记的VPAC癌基因受体特异性肽也适用于人乳腺恶性病变的NRI成像。TJU的其他研究人员也有类似的需求。我们现有的PET/SPECT/CT成像设备包括机构支持、辅助设备、动物模型和机构批准的方案。光学成像设备的增加将大大提高我们在天津大学的研究能力。 公共卫生相关性：将实验室发现转化为临床诊断和治疗的转化生物医学研究严重依赖于分子研究。拟议的光学成像设施将使我们的生物医学研究人员能够以协同和互补的方式进行非侵入性成像，加速从实验室到床边的过渡。

DESCRIPTION (provided by applicant): The importance of imaging small animals in basic and translational biomedical research, with such modalities as PET, SPECT, CT, optical, ultrasound, and MRI, cannot be over- emphasized. The ability to image small animals without sacrificing them, allows investigators to a) validate novel probes for diagnosis, b) conduct in vivo pharmacokinetic studies, c) evaluate investigational bio-molecules for prevention and therapy, and d) determine the effectiveness of therapy. Small animal imaging reduces the number of animals necessary for studies and controls cost, while providing scientifically valid and statistically significant data. At Thomas Jefferson University (TJU), there are more than 300 basic and physician scientists engaged in biomedical research in oncology, neurology, and cardiology. Four years ago, TJU established a small animal imaging facility that is directed by the PI in the Department of Radiology. The facility includes a CT, a PET/SPECT, and a PET scanner. This facility has thus far been used by 33 investigators and produced more than 30 articles in peer-reviewed journals. In longitudinal studies, animals receive radiation doses at variable levels and frequency. Concerns are raised regarding the unknown consequences of this radiation, particularly in such studies as effectiveness of therapeutic intervention, angiogenesis inhibition, and imaging apoptosis. At the same time, investigators realize that in optical imaging any fluorescent dye that compromises visualization of a lesion due to its depth in the body can be radiolabeled for PET or SPECT imaging. The roles of scintigraphic and optical imaging are complimentary, and we will use the two modalities synergistically. For example, a successful PNA construct developed in our laboratory that enables PET imaging of kRAS oncogene mRNA in xenografts when labeled with Cu-64 has been labeled with a near infrared (NIR) dye, NIR664, for successful optical imaging of human colorectal cancer xenografts in mice. Similarly, a Cu-64 labeled VPAC oncogene receptor specific peptide developed in our laboratory for human breast cancer imaging also lends itself for NRI imaging of malignant lesions in human breast. Other investigators at TJU demonstrate similar needs. Available to us with the existing PET/SPECT/CT imaging facility are the institutional support, ancillary devices, animal models, and institutionally approved protocols. The addition of optical imaging facility will strongly enhance our research capability at TJU. PUBLIC HEALTH RELEVANCE: Translational biomedical research in which laboratory discoveries are translated into clinical diagnosis and treatment relies heavily on molecular research. The proposed optical imaging facility will enable our biomedical investigators to perform non-invasive imagining in a synergistic and complementary fashion accelerating the bench to bedside transition.