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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 (from CRISP网站） 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对于最佳管理至关重要。正电子发射断层扫描是一种更敏感的技术，用于识别纵隔淋巴结转移，但有费用和缺乏可用性的缺点。我们的方法来开发一个敏感的，更容易获得的成像测试是探索一个更合适的载体分子，这是关键实现交付的放射性药物探针所需的目标问题。为此，我们利用放射性碘化磷脂类似物（PLE）作为潜在的诊断成像剂。这些脂质类似物由于不能被代谢和清除而选择性地保留在肿瘤膜中。在临床前研究中，我们已经证明这些分子在多种鼠和人肿瘤中具有高水平的选择性蓄积，包括SCID小鼠中的人NSCLC模型（A549）。本提案的目的是生成关于使用第二代PLE类似物NM-404对NSCLC患者进行成像的初步人体数据。本提案的具体目的是：1）确定放射性标记的I-131 NM-404在10例NSCLC患者中的最佳成像特征。将确定药代动力学、辐射剂量测定、生物分布和最佳成像时间。2)确定NM-404在5名接受切除术的患者中收集的NSCLC肿瘤中的特异性肿瘤蓄积和代谢命运。3)收集10例可评价疾病患者的NSCLC肿瘤成像的初步数据。由于有利的疗效、毒性（两种动物种属，200倍预期成像剂量）和剂量测定结果，最近提交了IND，以评价NM-404在人类前列腺癌患者中的作用。该探索性研究的结果将为更大规模的研究提供初步数据，该研究旨在更准确地估计NM-404对NSCLC分期和/或治疗后反应的预测能力。

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. (from CRISP website) 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.