Large Volume Intratumoral Injection Device for Therapeutic Liver Infusions

用于治疗性肝脏输注的大容量瘤内注射装置

• 批准号: 9246698
• 负责人: Jim Stice
• 金额: $ 4万
• 依托单位: TWIN STAR TDS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9246698
• 关键词: Ablation; Anatomy; Animal Model; Animals; Area; Caliber; Canis familiaris; Carcinoma; Catheters; Chemicals; Chemoembolization; Cirrhosis; Clinical; Cytotoxic agent; Data; Development; Devices; Diagnosis; Disease; Doxorubicin; Drug Delivery Systems; Drug resistance; Economics; Encapsulated; Ensure; Ethanol; Fiber; Gadopentetate Dimeglumine; General Population; Health; Hepatitis C; Human; Implant; Incidence; Infusion procedures; Injection of therapeutic agent; Lead; Length; Link; Liver; Liver neoplasms; Malignant neoplasm of liver; Methodology; Minority; Modeling; Morbidity - disease rate; Needles; New Zealand; Operative Surgical Procedures; Oryctolagus cuniculus; Partial Hepatectomy; Patients; Penetration; Performance; Phase; Preclinical Testing; Prevalence; Primary carcinoma of the liver cells; Process; Prostate; Protocols documentation; Radioembolization; Recurrence; Regulatory Pathway; Research; Resources; Solid Neoplasm; Surface; Survival Rate; System; Technology; Therapeutic; Therapeutic Agents; Tissues; Transplantation; Treatment Efficacy; Tumor Pathology; Tumor Tissue; United States; cancer cell; cell growth; chemotherapeutic agent; commercialization; contrast imaging; curative treatments; cytotoxic; drug distribution; improved; in vivo; innovation; interest; intrahepatic cancer; liver transplantation; minimally invasive; neoplastic; novel; standard of care; treatment planning; tumor

 DESCRIPTION (provided by applicant): The objective of this proposal is to demonstrate the feasibility of an innovative injection device (proposed product) to improve upon intratumoral delivery of liver therapeutics as compared to standard injection needles currently used. Hepatocelluar carcinoma (HCC) will become an increasing burden on economic resources in the coming years as the prevalence of cirrhosis due to multiple disease processes in the general population increases. Transplant and surgical treatment are well established and have provided satisfactory overall survival for eligible patients, however only a small minority of HCC patients are eligible for these therapies. Therefore considerable efforts have been directed toward developing alternative minimally invasive treatments. HCC therapeutic delivery by direct injection has the potential to significantly reduce the expense and morbidity of current therapeutics or those in development. Though direct injection is a seemingly straightforward approach to the problem, limited ability to inject tumors greater than 3cm in diameter and uneven distribution of the therapeutic after injection, are significant drawbacks to direct injectin. In contrast to conventional injection needles, the proposed injection device is porous along the entire length of the targeted anatomy; therefore, the surface area of tissue in contact with infusate is considerably increased. Hypothesis: Improved infusate delivery will lead to a larger area and more uniform distribution of infusate within the tumor tissue and lend itself to enhanced therapeutic direct intratumoral injection protocols for various chemoablative and anti- neoplastic infusates. Preliminary Data: We have demonstrated that porous injection devices have significantly improved in vivo distribution of ethanol within normal canine prostates and other studies have demonstrated the unique performance benefits of applicant's porous injection device. Specific Aim: This project entails preclinical testing of the porous injection device for eventual application to human patients with intrahepatic tumors. Aim 1. Demonstrate that the porous injection device provides broader distribution of an infusate compared to a standard needle. Task 1 - Transfer of VX-2 Cells and growth of tumor in rabbit for tumor implant tissue. Task 2 - Determine the preferred flow rate for infusate into the VX-2 tumor in rabbit liver Task 3 - Comparison of concentration and distribution of infusate components after infusion into VX-2 tumor with porous device and standard needle. Milestone: The porous injection device will show 50% greater distribution as compared to needle injection.

 描述（由申请方提供）：本提案旨在证明与目前使用的标准注射针相比，创新注射器械（申报产品）改善肝脏治疗药物瘤内输送的可行性。在未来几年中，由于一般人群中多种疾病过程导致的肝硬化的患病率增加，肝细胞癌（HCC）将成为经济资源的日益增加的负担。移植和手术治疗已经得到了很好的确立，并为符合条件的患者提供了令人满意的总生存率，但只有少数HCC患者符合这些治疗的条件。因此，相当大的努力已经指向开发替代的微创治疗。通过直接注射的HCC治疗递送具有显著降低当前治疗剂或开发中的治疗剂的费用和发病率的潜力。虽然直接注射是一种看似简单的方法，但注射直径大于3cm的肿瘤的能力有限，注射后治疗剂的分布不均匀，是直接注射的显著缺点。与常规注射针相比，所提出的注射装置沿目标解剖结构的整个长度沿着是多孔的;因此，与输注物接触的组织的表面积显著增加。假设：改进的输注物递送将导致肿瘤组织内的更大面积和更均匀的输注物分布，并有助于增强用于各种化学消融和抗肿瘤输注物的治疗性直接肿瘤内注射方案。初步数据：我们已经证明多孔注射装置显著改善了乙醇在正常犬前列腺内的体内分布，并且其他研究已经证明了申请人的多孔注射装置的独特性能益处。具体目标：该项目需要对多孔注射装置进行临床前测试，以最终应用于患有肝内肿瘤的人类患者。目标1.证明与标准针头相比，多孔注射装置可提供更广泛的输注液分布。任务1 -VX-2细胞的转移和肿瘤在兔体内的生长，用于肿瘤植入组织。任务2 -确定输注到兔肝脏VX-2肿瘤中的优选流速任务3 -比较用多孔装置和标准针头输注到VX-2肿瘤中后输注液组分的浓度和分布。里程碑：多孔注射器械的分布比针头注射多50%。