Integrated Image-Guided Targeted Therapy for Refractory Ovarian Cancer

难治性卵巢癌的综合影像引导靶向治疗

• 批准号: 8633430
• 负责人: Mansoor M Amiji
• 金额: $ 66.56万
• 依托单位: NEMUCORE MEDICAL INNOVATIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8633430
• 关键词: Address; Adverse effects; Basic Science; Cancer Model; Cancer Patient; Clinic; Clinical; Clinical Trials; Complex; Contrast Media; Data; Diagnostic; Disease Progression; Distal; Dosage Forms; Dose; Drug Kinetics; Epithelial ovarian cancer; Folate; Gadolinium; Goals; Human; Image; In Vitro; Investigation; Knowledge; Laboratories; Light; Link; Localized Disease; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of ovary; Medicine; Modality; Modeling; Morphology; Multi-Drug Resistance; Mus; Nanotechnology; Neoplasm Metastasis; Newly Diagnosed; Normal tissue morphology; Outcome; Paclitaxel; Pharmaceutical Preparations; Phenotype; Plasma; Polysorbate 80; Rattus; Recurrence; Recurrent Malignant Neoplasm; Recurrent disease; Recurrent tumor; Refractory; Regimen; Research Personnel; Safety; Solutions; System; Technology; Therapeutic Agents; Time; Tissues; Toxic effect; Transgenic Mice; Translating; Treatment Efficacy; Treatment Protocols; Validation; Xenograft procedure; base; cancer therapy; chemotherapeutic agent; combat; cytotoxicity; design; docetaxel; effective therapy; exhaust; experience; gadolinium oxide; human FOLR1 protein; improved; in vivo; innovation; insight; intraperitoneal; malignant breast neoplasm; man; mortality; mouse model; nanocarrier; nanoemulsion; nanomedicine; novel; ovarian neoplasm; preclinical study; residence; tumor; uptake

DESCRIPTION (provided by applicant): During treatment recurrent cancers build up multidrug resistance to conventional and novel chemotherapeutic agents representing a formidable challenge in clinical cancer therapy, especially for the effective treatment of gynecological malignancies. This R01 proposal describes a targeted-, combination imaging agent and therapeutic nanoemulsion, designated NMI-500, designed to provide timely diagnostic information on where the co-deliver treatment is accumulating and provide clinicians the quantitative insight to adjust treatment schedules in light of this new information. A team of investigators from two commercial and two academic organizations will collaborate to develop this clinically translatable strategy, initially addressing recurrent multidrug resistant phenotype. NMI-500 uses folate to specifically target docetaxel (DTX), and gadolinium (Gd) an MR imaging agent to localized disease as well as distal metastases. NMI-500's targeting moiety folate is known to improve uptake by tumors expressing folate receptor alpha (FR-a). FR- a, largely absent from normal tissue, has been shown to be over expressed on >80% of recurring ovarian tumors. In breast cancer high FR-an expression has been linked to poor clinical outcomes. The imaging component of NMI-500 will be achieved with the MRI contrast agent Gd, which has been shown to enhance contrast efficiency when conjugated to a nanoemulsion.1 Specific aims will assess and validate the imaging, targeting, efficacy and pharmacokinetics of the combination imaging/chemotherapeutic product, NMI-500.

描述(申请人提供)：在治疗期间，复发癌症对传统和新型化疗药物产生多重耐药性，这是临床癌症治疗中的一个巨大挑战，特别是对妇科恶性肿瘤的有效治疗。这份R01提案描述了一种名为NMI-500的靶向、组合显像剂和治疗性纳米乳剂，旨在提供有关联合治疗在哪里积累的及时诊断信息，并为临床医生提供量化洞察，以根据这些新信息调整治疗计划。来自两个商业组织和两个学术组织的研究小组将合作开发这一临床可翻译的策略，最初解决复发的多药耐药表型。NMI-500使用叶酸来特异性地靶向多西紫杉醇(DTX)，并使用Gd(一种磁共振成像剂)来定位疾病以及远端转移。已知，以部分叶酸为靶点的NMI-500‘S可促进表达叶酸受体α(FR-a)的肿瘤的摄取。在正常组织中大部分缺失的FR-a已被证明在80%的复发性卵巢肿瘤中过度表达。在乳腺癌中，高FR-α的表达与不良的临床结果有关。NMI-500的成像成分将通过核磁共振造影剂Gd实现，已被证明在与纳米乳剂1结合时可以提高对比度效率。1具体目标将评估和验证组合成像/化疗产品NMI-500的成像、靶向、疗效和药代动力学。