MR RECEPTOR IMAGING

本提案的总体目标是描述和评价 用于受体成像的磁共振（MR）药物。 这些 所提出的药剂应改善组织选择性， 癌症是美国第二大常见的死亡原因， States. 超顺磁性氧化铁（SPIO）颗粒具有高的 弛豫率使得通过MR进行可行的受体成像商业化 然而，现有的SPIO制剂要么太大， 经毛细血管通过（例如，AMI-25）或不易形成稳定 具有载体分子如多肽的化合物（例如，AMI-227）。 这项研究的基础是由我们最近的发现形成的。 单晶氧化铁纳米化合物（MION）的实验室， 容易通过非共价键连接到各种载体分子上 结合并因此被递送至体内受体位点并被检测 MR成像。 该提案的目的是扩大以前的 MR受体成像研究的可行性研究。 的范围 研究包括物理和生物化学表征的 母体化合物（MION）和MION靶向不同受体， 肝细胞和胰腺细胞。 MION的小尺寸（2.86 +/- 0.9 nm），这有助于跨毛细血管通道，导致相对 体外低弛豫率。 一个更戏剧性的效果，然而，观察到， vivo. 这项研究的一个独特组成部分将测试假设， 在体内发生颗粒聚集， 弛豫率 这些药物的临床前效用将在 体内动物模型和体外良性和恶性研究 人体组织 本研究的长期目标是：a）改善 检测癌症，和B）允许测定 vivo. 预期受体靶向MR造影剂可 最终取代或补充非特异性间质和RES 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.