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使 淋巴瘤和白血病的治疗研究取得令人鼓舞的结果。 在这些研究中获得的定量成像数据也 确定了几个问题，这些问题对于提高 向肿瘤组织传递的辐射与正常组织相比，以便 增强治疗效果。我们建议通过以下方式解决这些问题 首先评估抗体的相对生物分布 人肿瘤移植瘤在SCID小鼠体内的内化或非内化 以及以正常器官为靶点，并测试其优势 将抗体与替代放射性标记结合将导致 细胞内放射性滞留(目标1和2)。我们还将 开发定量成像方法以替代治疗方法 放射性同位素为放射性标记抗体提供准确的评估 患者体内的生物分布(目标3)。基于这些临床前研究的结果 实验中，我们将选择替代的放射性核素抗体组合 与项目一和项目二(目标4)目前使用的方案进行比较。

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).