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来检测和区分侵袭性病变和惰性病变，以便在癌症发展的早期阶段治疗患者。同样重要的是评估治疗效果 治疗针对分子靶标，例如酶抑制或干扰特定途径。 新的加州大学圣地亚哥分校摩尔斯癌症中心 (MCC) 的中央空间还设有我们的啮齿动物成像设施，毗邻动物园，ICMIC 团队将与其他癌症研究人员聚集在一起。我们在 MCC 内与 NCI 资助的纳米肿瘤中心一起建立了 ICMIC，以最大限度地提高效率和协同作用。 五年前的 P20 奖项开始了我们的多学科合作。在过去五年中，我们在 P50 提交的 R01 类型项目中提交了 10 多个新想法，在 P20 和 P50 提交中提交了许多开发项目。其中 8 个想法（7 个项目和 1 个开发项目）现已获得 NIH、DOD 或 DOE 的资助。我们在此展示 5 个新项目和一个之前提交的已修改项目。此 P50 申请中提交的项目重点关注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， 与超声造影剂。他们计划利用氟碳乳液只有在组合时才可见的事实，以在乳液暴露于感兴趣的酶时诱导聚集。项目 2 旨在标记一种携带铂的聚合物，用于目前正在进行临床试验的癌症化疗药物的 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 受体来提高药物的治疗指数。项目 3 提出了一种巧妙的纳米颗粒自组装系统，用于靶向血管生成（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症的细胞标记、基因传递和光学成像的前沿研究。 我们还将本次 ICMIC 的重点放在职业发展上，并介绍了三名申请者接受分子成像培训。一个主要项目和所有 3 个发展项目的 P.l.s 都是来自病理学 (1)、医学 (3) 和癌症中心 (1) 的初级教师，并由经验丰富的研究人员指导。 机构支持非常重要。我们在癌症中心提供了黄金空间，所有啮齿类动物成像设备都位于癌症中心的动物饲养场附近，并配备了关键人员。

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.