Radiolabeled Monoclonal Antibody Imaging Of Tumors & PET

这些抗体研究旨在发展检测和治疗恶性肿瘤的改进方法。我们的小组进行临床前评估放射标记抗体，似乎是有希望的初步筛选后。临床试验评价其药代动力学和剂量学是由我组完成的。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抗tac单克隆抗体。为了增加传递到肿瘤的放射性剂量并提高肿瘤与非肿瘤的比率，我们正在寻求一种预靶向方法，即带链帕霉素的抗体在没有任何放射性的情况下传递，在它靶向肿瘤后注入放射性标记的生物素。这使得放射性标记的小生物素迅速定位在肿瘤中或迅速排出。我们关注的两种抗体是B3和抗间皮素（由帕斯坦博士的实验室开发）。这些预靶向研究评估了Y-90和Bi-213。他的化学工作主要集中在球形聚合物（PAMAM树突状聚合物）的化学修饰，作为放射性核素和生物分子的载体。此外，白博士还开发了一种由NIH PET部门生产的Y-86的简单纯化方法。该Y-86计划用于Y-90放射标记抗体的剂量测定，目前我们小组正在使用该抗体。NCI外科分部（Dr. Libutti）正在使用[F-18] FDG在PET和[O-15]水中进行肿瘤检测、随访和血流测量的各种方案。有几个正在进行的合作研究评估氟脱氧葡萄糖- pet用于评估肿瘤对治疗的反应（Swain博士，Mackall博士，Sausville博士和Wilson博士）。我们已经评估了氟脱氧葡萄糖- pet在评估HIV患者病毒复制位点中的应用，并注意到艾滋病患者淋巴结可视化的有趣变化。Brust)。我们正在利用氟脱氧葡萄糖PET试图定位活化淋巴细胞的位置。在一项研究中，我们利用FDG-PET来评估活动性与非活动性系统性红斑狼疮患者的代谢活性部位。我们还评估了FDG-PET在自身免疫性淋巴细胞增生性综合征与恶性淋巴瘤患者之间的区分能力。

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.