NM-404 AS AN IMAGING AGENT IN PATIENTS WITH NON-SMALL CELL LUNG CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。非小细胞肺癌（NSCLC）是当今美国癌症死亡的主要原因。准确的术前评估局部，区域和远处转移扩散是最佳管理的关键。正电子发射断层扫描是一种识别纵隔淋巴结转移的更敏感的技术，但更昂贵，并不是所有地方都可以使用。为了开发一种更灵敏、更容易获得的成像测试，我们将探索一种载体分子，将放射性药物问题传递到所需的目标组织。为此，我们将使用放射性碘化磷脂醚类似物（PLE）作为潜在的诊断显像剂。由于PLE无法被代谢和清除，它们被选择性地保留在肿瘤膜上。在临床前研究中，我们已经证明这些分子在多种小鼠和人类肿瘤中具有高水平的选择性积累，包括SCID小鼠的人类非小细胞肺癌模型（A549）。本研究可能：(1)确定10例非小细胞肺癌患者放射性标记I-131 NM-404的最佳影像学特征。将确定药代动力学、辐射剂量学、生物分布和最佳成像时间。(2)确定NM-404在5例切除的NSCLC肿瘤中的特异性肿瘤积累和代谢命运。(3)收集10例可评价疾病的NSCLC肿瘤影像学初步资料。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States today. Accurate preoperative assessment of local, regional and distant metastatic spread is criticial for optimal management. Positron emission tomography scanning is a more sensitive technique for identifying mediastinal nodal metastases, but is more expensive and is not available everwhere. To develop a sensitive, more readily available imaging test, we will explore a carrier molecule deliver a radiopharmaceutical proble to the desired target tissue. To do this, we will use on radioiodinated phospholipid ether analogs (PLE) as potential diagnostic imaging agents. The PLE's are selectively retained in tumor membranes due to their inability to become metabolized and cleared. In preclinical studies, we have shown these molecules have high levels of selective accumulation in a wide variety of murine and human tumors including a human NSCLC model (A549) in SCID mice. The study may: (1) Determine the optimal imaging characteristics of radiolabelled I-131 NM-404 in ten patients with NSCLC. The pharmacokinetics, radiation dosimetry, biodistribution, and optimal imaging times will be determined. (2) Determine the specific tumor accumulation and metabolic fate of NM-404 in NSCLC tumors collected in five patients undergoing resection. (3) Collect preliminary data on imaging NSCLC tumors in ten patients with disease that can be evaluated.