Image-Guided Interventional Cancer Therapy with Liposomal Radionuclides

图像引导脂质体放射性核素介入癌症治疗

• 批准号: 7694312
• 负责人: ANDE BAO
• 金额: $ 27.81万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-29 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7694312
• 关键词: Animals; Applications Grants; Behavior; Biological; Cancer Patient; Characteristics; Charge; Chemistry; Clinical; Collaborations; Convection; Development; Diagnosis; Diagnostic; Diffuse; Diffusion; Dose; Drug Delivery Systems; Drug Formulations; Drug or chemical Tissue Distribution; Electrons; Ensure; Environment; Epidermal Growth Factor Receptor; Equilibrium; Evaluation; Exclusion; Figs - dietary; Gel; Goals; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Histocytochemistry; Histopathology; Human; Image; Infusion Technique; Infusion procedures; Injection of therapeutic agent; Intellectual Property; Interventional radiology; Intravenous; Investigation; Investigational Therapies; Label; Laboratories; Lead; Legal patent; Length; Lipids; Liposomes; Local Therapy; Malignant Neoplasms; Measurement; Measures; Mediating; Medical; Medical Imaging; Methodology; Methods; Monitor; Nanotechnology; Normal tissue morphology; Nuclear; Nude Rats; Oral; Organ; Outcome; Paper; Particle Size; Pathology; Patients; Performance; Pharmaceutical Preparations; Photons; Physics; Pilot Projects; Planning Techniques; Protocols documentation; Radiation therapy; Radioactive; Radioactivity; Radioisotopes; Radiolabeled; Radionuclide therapy; Radiopharmaceuticals; Reporting; Reproducibility; Research; Research Personnel; Resolution; Resources; Rhenium; Rhenium 186; Route; Science; Site; Solid; Solid Neoplasm; Surface; Surgeon; System; Taiwan; Technetium 99m; Techniques; Technology; Testing; Theoretical model; Therapeutic; Therapeutic Effect; Time; Tissues; Toxic effect; Training; Translations; Travel; Treatment Efficacy; Treatment outcome; Tumor Pathology; Tumor Volume; X-Ray Computed Tomography; Xenograft Model; Xenograft procedure; base; cancer radionuclide therapy; cancer therapy; clinical application; dosimetry; drug distribution; experience; human tissue; improved; innovation; interstitial; irradiation; lymph nodes; member; multidisciplinary; nanoparticle; non-invasive monitor; novel; particle; public health relevance; radiation absorbed dose; radiotracer; research study; response; single photon emission computed tomography; small molecule; stem; therapeutic effectiveness; tumor; tumor eradication; tumor xenograft

DESCRIPTION (provided by applicant): Problem: Drug delivery to solid cancers via intravenous or oral infusion is generally inefficient, resulting in poor treatment outcomes for these cancers. An emerging strategy for overcoming this dilemma is the use of image- guided intratumoral drug infusion techniques. Yet, with this infusion route, achieving a homogeneous intratumoral drug distribution is challenging. When therapeutic radionuclides are used in place of drugs, homogeneity of the intratumoral therapy is improved due to the cross-fire of beta emissions. Purpose: The long-term goals of this research are: 1) to develop an image-guided interventional cancer liposomal radionuclide therapy system, which includes the use of image-guidance and dose planning for effective tumor therapy, and the performance of interventional intratumoral therapy; and 2) to develop an optimal therapeutic radiopharmaceutical for this therapy. The hypothesis of this proposal is that ideal liposome radiopharmaceutical formulations will be discovered for optimized image-guided interventional cancer radionuclide therapy. Specific Aims are: 1) to determine intratumoral distribution and retention of liposomes of various liposome surface charges / sizes and with / without specific targeting to epidermal growth factor receptor (EGFR) after intratumoral infusion; 2) to determine the therapeutic effectiveness of rhenium-186 (Re-186)-liposomes in tumor xenografts in nude rats; and 3) to determine radiation absorbed dose distribution using dosimetry for liposomes carrying therapeutic radionuclides. Methods: Liposome formulations will be tested in head and neck squamous cell carcinoma (HNSCC) xenograft model in nude rats. Non-invasive nuclear imaging with technetium-99m (Tc-99m)-labeled liposomes will be used to determine intratumoral retention and the distribution of liposomes within the tumor. Therapeutic efficiency of optimal liposome formulations carrying the therapeutic radionuclide, Re-186 will also be determined. Tumor pathology/histochemistry will be correlated with caliper measured therapy response and its potential influence on drug delivery. As a crucial component for development of an effective Re-186-liposome radiopharmaceutical, dosimetry of Re-186 liposomes in tumors and normal organs will also be studied. Outcomes: A better understanding of the optimal liposome characteristics for intratumoral retention and distribution following intratumoral infusion will be determined. The relationship between intratumoral retention and distribution and tumor response will also be determined. This will provide a crucial step for translation of this solid tumor therapy into humans. Benefits: This project will advance the use of this new interventional cancer therapy technique to benefit patients with solid cancers. Public Health Relevance: Solid cancer therapy is greatly compromised by insufficient drug delivery to tumors to ensure tumor eradication. The proposed new solid cancer therapy technique uses advanced medical imaging to guide the direct delivery of therapeutic radionuclides to the solid cancer. This method will potentially benefit cancer patients by enhancing tumor drug concentrations and thereby improving tumor therapy while decreasing damage to normal tissue.

描述（由申请人提供）：问题：通过静脉输注或口服输注向固体癌症输送的药物通常效率低下，导致这些癌症的治疗结果不佳。克服这一困境的新兴策略是使用图像引导的肿瘤内药物输液技术。然而，通过这种输液途径，达到统一的肿瘤内药物分布具有挑战性。当使用治疗性放射性核素代替药物时，由于β排放的交叉射击，可以改善肿瘤内治疗的同质性。目的：这项研究的长期目标是：1）开发图像引导的介入式癌症脂质体放射性核素治疗系统，其中包括使用图像指导和剂量计划进行有效的肿瘤治疗，以及介入的肿瘤内治疗的性能； 2）为这种疗法开发最佳的放射性药物治疗。该提议的假设是，将发现理想的脂质体放射性药物制剂，以优化图像引导的介入式癌症放射性核素治疗。具体目的是：1）确定各种脂质体表面电荷 /尺寸的脂质体的肿瘤内分布和保留，并且在肿瘤内输注后具有 /无特定靶向表皮生长因子受体（EGFR）； 2）确定裸鼠肿瘤异种移植物中Rhenium-186（RE-186） - 唇下部的治疗有效性； 3）使用剂量测定法确定携带治疗放射性核素的脂质体的辐射吸收剂量分布。方法：脂质体配方将在裸鼠中的头颈部鳞状细胞癌（HNSCC）异种移植模型中进行测试。使用Technetium-99M（TC-99M）标记的脂质体的非侵入性核成像将用于确定肿瘤内保留率和在肿瘤内的脂质体分布。还将确定带有治疗性放射性核素的最佳脂质体配方的治疗效率，RE-186也将确定。肿瘤病理/组织化学将与卡尺测量的治疗反应及其对药物递送的潜在影响相关。作为开发有效的RE-186-脂质体放射性药物的关键成分，还将研究肿瘤和正常器官中RE-186脂质体的剂量测定法。结果：将确定对肿瘤内输注后的肿瘤内保留和分布的最佳脂质体特征的更好理解。肿瘤内保留与分布与肿瘤反应之间的关系也将得到确定。这将为将这种实体瘤疗法转化为人类提供关键步骤。好处：该项目将推动这种新的介入癌症治疗技术的使用，以使固体癌症患者受益。 公共卫生相关性：固体癌症疗法受到对肿瘤的药物递送不足以确保消除肿瘤的严重损害。提出的新的固体癌症治疗技术使用先进的医学成像来指导将治疗性放射性核素直接递送至固体癌症。该方法将通过促进肿瘤药物浓度并从而改善肿瘤治疗，同时减少对正常组织的损害，从而有可能使癌症患者受益。