MR RECEPTOR IMAGING

该提案的总体目标是描述和评估 用于受体成像的磁共振(MR)药物。这些 建议的药物应提高组织选择性，从而增强 癌症是美国第二大最常见的死亡原因 各州。超顺磁性氧化铁(SPIO)颗粒具有-高 松弛使MR先生商业上可行的受体成像 然而，可用的SPIO制剂要么太大，不能 通过毛细管通道(例如，AMI-25)或不容易形成稳定 具有载体分子的化合物，例如多肽(例如，AMI-227)。 这项研究的基础是我们的最新发现 单晶氧化铁纳米化合物(Mion)的实验室 以非共价形式很容易地与各种载体分子结合 结合，从而被传递到体内的受体位置并被检测到 通过核磁共振成像。这项提案的目的是延长以前的 磁共振受体成像研究的可行性研究。的范围 研究包括物理和生化特性的研究 母体化合物(Mion)和针对不同受体的Mion 肝细胞和胰腺细胞。Mion的小尺寸(2.86+/-0.9 Nm)，这促进了跨毛细管通过，导致了相对 体外松弛系数低。然而，观察到的一个更戏剧性的效果是 活着。这项研究的一个独特部分将检验这一假设 粒子在体内聚集，导致更高的组织 放松。这些药物的临床前效用将在#年进行评估。 体内动物模型和体外研究中的良恶性 人体组织。这项研究的长期目标是：a)改进 癌症的检测，以及b)允许在 活着。预计以受体为靶点的MR造影剂可以 最终取代或补充非特异性间质和RE 用于癌症检测和肿瘤治疗监测的造影剂。

The overall goal of this proposal is to characterize and evaluate magnetic resonance (MR) pharmaceuticals for receptor imaging. These proposed agents should improve tissue selectivity and thus enhance detection of cancer, the second most common cause of death in the United States. Superparamagnetic iron oxide (SPIO) particles possess-high relaxivity to make feasible receptor imaging by MR. Commercially available SPIO preparations, however, are either too large for transcapillary passage (e.g., AMI-25) or do not readily form stable compounds with carrier molecules such as polypeptides (e.g., AMI-227). The basis of this research is formed by the recent discovery in our laboratory of a monocrystalline iron oxide nanocompound (MION) that can be readily attached to a variety of carrier molecules by noncovalent binding and thus be delivered to receptor sites in vivo and be detected by MR imaging. The intent of this proposal is to extend previous feasibility studies in MR receptor imaging research. The scope of the research includes the physical and biochemical characterization of the parent compound (MION) and MION targeted to different receptors on hepatocytes and pancreatic cells. The small size of MION (2.86 +/- 0.9 nm), which facilitates transcapillary passage, results in a relatively low relaxivity in vitro. A more dramatic effect, however, is observed in vivo. A unique component of this research will test the hypothesis that clustering of particles occurs in vivo resulting in higher tissue relaxivity. The preclinical utility of these agents will be assessed in vivo in animal models and in vitro in studies of benign and malignant human tissue. The long term goals of this research are to: a) improve the detection of cancer, and b) allow determination of organ function in vivo. It is anticipated that receptor targeted MR contrast agents may ultimately replace or complement the nonspecific interstitial and RES contrast agents for cancer detection and tumor therapy monitoring.