Optical imaging for Translational Cancer Research

描述(申请人提供)：小动物成像在基础和转化性生物医学研究中的重要性，如PET、SPECT、CT、光学、超声和MRI，怎么强调都不为过。能够在不牺牲小动物的情况下对小动物进行成像，使研究人员能够a)验证用于诊断的新探针，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所需的动物数量并控制了成本，同时提供了科学上有效的和统计上有意义的数据。在托马斯·杰斐逊大学(TJU)，有300多名基础和内科科学家从事肿瘤学、神经学和心脏病学的生物医学研究。四年前，TJU建立了一个小型动物成像设施，由放射科的PI指导。该设施包括一台CT、一台PET/SPECT和一台PET扫描仪。到目前为止，这一设施已被33名调查人员使用，并在同行评议的期刊上发表了30多篇文章。在纵向研究中，动物受到不同水平和频率的辐射剂量。人们对这种辐射的未知后果提出了担忧，特别是在治疗干预的有效性、血管生成抑制和细胞凋亡成像等研究中。与此同时，研究人员意识到，在光学成像中，任何由于其在体内的深度而影响病变可视化的荧光染料都可以被放射性标记用于PET或SPECT成像。闪烁成像和光学成像的作用是互补的，我们将协同使用这两种模式。例如，我们实验室开发的一种成功的PNA构建体，当用铜-标记时，它能够对异种移植瘤中的KRAS癌基因mRNA进行PET成像，并且已经被近红外(NIR)染料NIR664标记，用于成功地在小鼠体内对人结直肠癌异种移植瘤进行光学成像。同样，我们实验室开发的用于人乳腺癌显像的铜-标记的Vpac癌基因受体特异性多肽也适用于人乳腺恶性病变的核磁共振成像。TJU的其他调查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增强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在很大程度上依赖于分子研究。拟议的光学成像设备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，加速从工作台到床边的过渡。

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.