In Vivo Cellular and Molecular Imaging Centers (ICMICs)

加州大学圣地亚哥分校致力于开发分子和细胞水平的体内成像，以回答基本的分子生物学问题，确定药物作用、相互作用和耐药性的分子基础，评估治疗干预的效果，并在一般疾病，特别是癌症的分子水平上探索独特的动物模型。最终目标是开发新的诊断和治疗工具，以检测和区分侵袭性和惰性病变，以便在癌症发展的早期阶段治疗患者。同样重要的是在以下情况下评估治疗效果 治疗针对的是分子靶点，如酶抑制或干扰特定途径。 新的摩尔斯加州大学圣迭戈分校癌症中心(MCC)的中央空间也是我们毗邻卵巢的啮齿动物成像设施的所在地，这将使ICMIC团队与其他癌症研究人员组成一个小组。我们已经在MCC内建立了ICMIC和NCI资助的纳米肿瘤中心，以最大限度地提高效率和协同效应。 五年前的P20奖开始了我们的多学科合作。在过去的五年里，我们在P50提交了10多个新想法作为R01类型的项目，并在P20和P50提交了许多开发项目。其中8个想法(7个项目和1个发展项目)现在已经得到了美国国立卫生研究院、美国国防部或美国能源部的资助。我们在这里介绍5个新的项目和一个以前提交的已经修订的项目。在这份P50申请中提交的项目侧重于成像和治疗之间的接口。项目1旨在检测肿瘤中的基质金属蛋白酶，这是肿瘤侵袭性的标志， 使用超声造影剂。他们计划利用这样一个事实，即氟碳乳剂只有在乳剂接触到感兴趣的酶时才能看到，当它们结合在一起时才能诱导聚集。项目2旨在标记一种载铂聚合物，用于目前处于临床试验中的一种癌症化疗药物的PET和SPECT成像。他们的目标是为临床医生提供药物动力学，并建议通过将其作为维生素B-12受体的靶点来增加该药物的治疗指数。项目3提出了一种聪明的纳米颗粒自组装系统，以靶向血管生成，这也是肿瘤侵袭性的标志，用于成像和治疗。开发项目代表了专注于干细胞癌的细胞标记、基因传递和光学成像的尖端研究。 我们还将重点放在职业发展方面，并介绍三名分子成像培训的申请者。一个重大项目和所有三个开发项目的PL.s都是来自病理学(1)、医学(3)和癌症中心(1)的初级教员，他们由经验丰富的调查人员指导。 制度支持意义重大。我们已经在癌症中心提供了黄金空间，所有啮齿动物成像设备都位于癌症中心毗邻卵巢的地方，并有关键人员。

The Unviersity of California, San Diego is committed to developing in-vivo imaging at the molecular and cellular level to answer basic molecular biology questions, to determine the molecular basis of drug action, interaction and resistance, to assess the effect of therapeutic interventions and to probe unique animal models at the molecular level of disease in general, and cancer in particular. The ultimate goal is to develop new diagnostic and therapeutic tools to detect and distinguish aggressive from indolent lesions in order to treat patients at the early stages of cancer development. Also critical is to assess therapeutic effects when therapy is directed at molecular targets such as enzyme inhibition or interference with specific pathways. The centralized space in the new Moores UCSD Cancer Center (MCC) that also houses our rodent imaging facility adjacent to the vivarium will group the ICMIC team with other cancer investigators. We have built the ICMIC along side the NCI funded NanoTumor Center within the MCC to maximize efficiency and synergism. The P20 award 5 years ago began our multidisciplinary collaboration. Over the last five years we have submitted more than 10 new ideas as R01-type projects in the P50s and many development projects in the P20 and P50 submissions. Eight of those ideas (7 for projects and 1 developmental project) have now been funded by the NIH, DOD, or DOE. We present here 5 new projects and one that was submitted previously that has been revised. The projects submitted in this P50 application focus on the interface between imaging and therapy. Project 1 aims to detect matrix metalloproteinase in tumors, a sign of tumor aggressiveness, with ultrasound contrast agents. They plan to take advantage of the fact that fluorocarbon emulsions are visible only when combined to induce aggregation at the time the emulsion is exposed to the enzyme of interest. Project 2 aims to label a platinum carrying polymer for PET and SPECT imaging of a cancer chemotherapeutic currently in clinical trial. Their goal is to provide the clinicians with drug kinetics and propose to increase the agent's therapeutic index by targeting it as the vitamin B-12 receptor. Project 3 proposes a clever nanoparticle self-assembly system to target angiogenesis, also a sign of tumor aggressiveness, for imaging and therapy. The Developmental Projects represent cutting edge research that focus on cell labeling, gene delivery, and optical imaging of stem cell cancers. We also focus this ICMIC on Career Development and present three applicants for training in molecular imaging. The P.l.s of one major project and all 3 Developmental Projects are junior faculty from Pathology (1), Medicine (3) and the Cancer Center (1) that are mentored by seasoned investigators. The Institutional support is significant. We have been provided prime space in the cancer center, all rodent imaging equipment are located in the cancer center adjacent to the vivarium, and key personnel.