Radiolabeled Monoclonal Antibody Imaging Of Tumors & PET

肿瘤放射性标记单克隆抗体成像

• 批准号: 6844208
• 负责人: JORGE A. CARRASQUILLO
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6844208
• 关键词: antitumor antibody; blood flow measurement; clinical trials; deoxyglucose; diagnosis design /evaluation; human subject; human therapy evaluation; immunologic substance development /preparation; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer radioimmunotherapy; neoplasm /cancer radionuclide diagnosis; nuclear medicine; patient oriented research; pharmacokinetics; positron emission tomography; radiation dosage; radiation therapy dosage; radionuclide imaging /scanning; radionuclides; radiopharmacology

These antibody studies are designed to develop improved methods for detecting and treating malignancies. Our group performs preclinical evaluation of radiolabeled antibodies that appear to be promising after initial screening. The clinical trials evaluating their pharmacokinetics and dosimetry are performed by our group. Two collaborative radioimmunotherapy trial with Dr. Waldmann (PI), in which we used humanized anti-tac monoclonal antibody, are ongoing. In order increase the radioactive dose delivered to tumors and improve the tumor to non-tumor ratios we are pursuing a pretargeting approaches were the antibody with strepavidin is delivered without any radioactivity and after it targets the tumor a radiolabeled biotin is injected. This allows the small radiolabeled bioitin to rapidly localize in tumor or be rapidly excreted. The 2 antibodies we have focused on are B3 and anti-mesothelin (developed in Dr. Pastan's lab).These pretargeting studies have evaluated Y-90 and Bi-213. Dr. Paik has focused his chemistry work on the chemical modification of spherical polymers (PAMAM dendrimers) as carriers of radionuclides and biological molecules. In addition Dr. Paik and has developed a simple purification method for Y-86 that is produce by the NIH PET department. This Y-86 is planned to be used for dosimetry of antibodies radiolabeled with Y-90 that are currently being used by our group. Various protocols using [F-18] FDG in PET and [O-15] water for tumor detection, followup, and blood flow measurements are ongoing with NCI surgery Branch (Dr. Libutti). There are several ongoing collaborative studies evaluating fluorodeoxyglucose-PET for assessing tumor response to treatment (Dr. Swain, Dr. Mackall, Dr. Sausville and Dr. Wilson). We have evaluated the use of fluorodeoxyglucose-PET in assesing sites of viral replication in patients with HIV and have noted intersting changes in nodal visualization in patients with AIDs(Dr. Brust). We are utilizing fluorodeoxyglucose PET in attemps to localize sites of activated lymphomcytes. In one study we utilized FDG-PET to evaluate sites of metabolic activity in patients with systemic lupus erythematosus with active versus inactive disease. We are also evaluting the ability of FDG-PET to differentiate between patients with benign versus lymphomatous adenopathy in the setting of autoimmune lymphoprolifertive syndrome versus.

这些抗体研究旨在开发检测和治疗恶性肿瘤的改进方法。我们的小组对放射性标记抗体进行了临床前评估，这些抗体在初步筛选后似乎很有希望。评估其药代动力学和剂量测定的临床试验是由我们小组进行的。两项与 Waldmann 博士（PI）合作的放射免疫治疗试验正在进行中，其中我们使用了人源化抗 tac 单克隆抗体。为了增加递送至肿瘤的放射性剂量并改善肿瘤与非肿瘤的比率，我们正在寻求一种预靶向方法，即在没有任何放射性的情况下递送具有链霉亲和素的抗体，并在靶向肿瘤后注射放射性标记的生物素。这使得小的放射性标记生物素能够快速定位在肿瘤中或被快速排出。我们重点关注的 2 种抗体是 B3 和抗间皮素（在 Pastan 博士的实验室开发）。这些预靶向研究评估了 Y-90 和 Bi-213。白南准博士的化学工作重点是作为放射性核素和生物分子载体的球形聚合物（PAMAM 树枝状聚合物）的化学改性。此外，Paik 博士还开发了一种简单的 Y-86 纯化方法，该方法由 NIH PET 部门生产。该 Y-86 计划用于我们小组目前使用的 Y-90 放射性标记抗体的剂量测定。 NCI 外科分部（Libutti 博士）正在使用 PET 中的 [F-18] FDG 和 [O-15] 水进行肿瘤检测、随访和血流测量的各种方案。有几项正在进行的合作研究评估氟脱氧葡萄糖 PET 来评估肿瘤对治疗的反应（Swain 博士、Mackall 博士、Sausville 博士和 Wilson 博士）。我们评估了氟脱氧葡萄糖-PET 在评估 HIV 患者病毒复制位点方面的应用，并注意到艾滋病患者淋巴结可视化的有趣变化（Brust 博士）。我们正在尝试利用氟脱氧葡萄糖 PET 来定位活化淋巴细胞的位点。在一项研究中，我们利用 FDG-PET 来评估患有活动性与非活动性疾病的系统性红斑狼疮患者的代谢活动部位。我们还在评估 FDG-PET 区分自身免疫性淋巴组织增生综合征和淋巴瘤性淋巴结病患者的能力。