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（由申请人提供）：在治疗期间，复发性癌症在临床癌症治疗中代表了巨大挑战的传统和新型化学治疗剂的多药耐药性，尤其是为了有效治疗妇科恶性肿瘤。该R01提案描述了指定为NMI-500的靶向组合成像剂和治疗性纳米乳液，旨在提供及时的诊断信息，以介绍共同服务器的累积何处，并为临床医生提供定量洞察力，以根据这些新信息来调整治疗时间表。来自两个商业和两个学术组织的一个调查人员团队将合作制定这种临床上可翻译的策略，最初解决反复的多药耐药表型。 NMI-500使用叶酸特异性靶向多西他赛（DTX），而Gadolinium（GD）是局部疾病和远端转移的MR成像剂。已知NMI-500的靶向部分叶酸可以通过表达叶酸受体α（FR-A）的肿瘤改善摄取。 Fr- A，很大程度上没有正常组织，已证明在> 80％的复发性卵巢肿瘤上表达过度。在乳腺癌中，高fr-An表达与临床结果不佳有关。 NMI-500的成像成分将通过MRI对比剂GD实现，在与纳米乳液结合时已证明可以提高对比度的效率。1具体目标将评估和验证组合成像/化学成像/化学型产品的成像，靶向，靶向，功效和药代动力学，NMI-I-500。