RADIOLABELLED ANTIBODY BIODISTRIBUTION, INTERNAL DOSIMETRY/RADIOTHERAPY

我们在放射性标记抗体治疗方面的丰富经验， 在淋巴瘤和白血病的治疗研究中取得了令人鼓舞的结果。 在这些研究中获得的定量成像数据也 确定了几个关键问题，以提高相对数量的 与正常组织相比，递送到肿瘤的辐射， 增强治疗效果。我们建议采取以下措施处理这些问题： 首先评估抗体的相对生物分布， 在SCID小鼠中使用人肿瘤异种移植物内化或未内化 以及正常器官作为靶点， 将抗体与替代性放射性标记结合， 放射性的细胞内滞留（目的1和2）。我们还将 开发定量成像方法， 放射性同位素，以提供放射性标记抗体的准确评估 患者体内的生物分布（目的3）。根据这些临床前研究的结果， 实验中，我们将选择替代放射性核素抗体组合 与项目I和II（目标4）目前使用的标准进行比较。

Our extensive experience with radiolabeled antibody therapy has led to encouraging results in studies of the therapy of lymphoma and leukemia. The quantitative imaging data obtained in these studies have also identified several issues critical for improving the relative amount of radiation delivered to tumor compared to normal tissues in order to augment the therapeutic effect. We propose to address these issues by first assessing the relative biodistribution of antibodies that are internalized or not internalized using human tumor xenografts in SCID mice as well as normal organs as targets, and testing the advantage of conjugating antibodies with alternative radiolabels that will lead to intracellular retention of radioactivity (Aims 1 and 2). We will also develop quantitative imaging methods for alternative therapeutic radioisotopes to provide accurate assessment of radiolabeled antibody biodistribution in patients (Aim 3). Based on results of these preclinical experiments, we will select alternative radionuclide antibody combinations for comparison with those currently used in Projects I and II (Aim 4).