NM-404 A Novel Imaging Agent in Lung Cancer

描述（由申请人提供）：非小细胞肺癌（NSCLC）是 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对于 优化管理正电子发射断层扫描是一种更敏感的 用于识别纵隔淋巴结转移的技术，但 费用和缺乏可用性的缺点。我们处理 开发一种灵敏、更容易获得的成像测试是为了探索一种 更合适的载体分子，这是实现递送 放射性药物探针到所需的目标问题。为此，我们必须 利用放射性碘化磷脂类似物（PLE）作为潜在的 诊断显像剂。这些脂质类似物被选择性地保留在 肿瘤膜由于它们不能被代谢和清除而被破坏。在 临床前研究表明，这些分子具有高水平的 在多种鼠和人肿瘤中选择性蓄积，包括 人NSCLC模型（A549）。 本提案的目的是生成以下方面的初步人类数据： 使用第二代PLE类似物NM-404对患有 NSCLC。本建议的具体目标是：1）确定最佳 放射性标记的I-131 NM-404在10例 NSCLC。药代动力学、辐射剂量学、生物分布和最佳 将确定成像时间。2)确定特定肿瘤蓄积 NM-404在五名患者中收集的NSCLC肿瘤中的代谢命运 正在接受切除手术3)收集NSCLC肿瘤成像的初步数据， 10例可评价疾病患者。 由于良好的疗效，毒性（两种动物物种在200倍的 预期成像剂量）和剂量测定结果，最近提交了IND， 评估NM-404在人类前列腺癌患者中的作用。的结果 探索性研究将为更大规模的研究提供初步数据， 为了更准确地估计NM-404用于分期和/或 在NSCLC治疗后的反应。

DESCRIPTION (provided by applicant): 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 critical for optimal management. Positron emission tomography scanning is a more sensitive technique for identifying mediastinal nodal metastases, but has the disadvantage of expense and lack of availability. Our approach to the development of a sensitive, more readily available imaging test is to explore a more appropriate carrier molecule, which is key in achieving delivery of a radiopharmaceutical probe to the desired target issue. To do this, we have capitalized on radioiodinated phospholipid either analogs (PLE) as potential diagnostic imaging agents. These lipid analogues 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 objective of this proposal is to generate preliminary human data regarding the use of the second-generation PLE analog, NM-404 in imaging patients with NSCLC. The specific aims of this proposal are to: 1) Determine the optimal imaging characteristics of radiolabeled 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 evaluable disease. Due to favorable efficacy, toxicity (two animal species at 200 times the anticipated imaging dose), and dosimetry results, an IND was recently filed to evaluate NM-404 in human prostate cancer patients. The results of this exploratory study will provide the preliminary data for a larger study designed to more accurately estimate the predictive power of NM-404 for staging and/or following response to therapy in NSCLC.