TUMOR IMAGING WITH RADIOLABELED MONOCLONAL ANTIBODY

该补助金结合了一套综合的实验室科学和 临床研究特别侧重于改善 诊断成像和潜在治疗人类癌症的能力 使用放射性标记的单克隆抗体。 在目标1中，我们将开发 使用碘化的抗体放射性碘化的改进方法 酪胺-纤维二糖（TCB）加合物，旨在产生增加的 放射性碘在肿瘤中的滞留。 标签方法将是 优化了免疫反应性的产量和保存， 产品将在肿瘤细胞悬浮液和肿瘤细胞中进行测试。 小鼠 在目标2中，我们将尝试免疫特异性淋巴结造影 转移性黑色素瘤患者的肿瘤淋巴结。 我们有 证明了抗体在肿瘤节点的非特异性摄取;这 将被皮下注射的冷无关抗体阻断 在同时注射I-131特异性和I-125非特异性之前， 特异性抗体。 在I-131成像后，切除的淋巴结将 通过计数和双同位素放射自显影进行分析。 在目标3 我们将扩展我们的工作， 最终导致肺癌和乳腺癌。 使用诊断 我们将仔细测量I-131标记抗体的剂量， 生物分布和肿瘤标记，并估计内部 辐射吸收剂量 我们将确定， 放射性标记的抗体的成像和肿瘤沉积， 碘苯基和酪胺-纤维二糖方法相比， 氯胺-T标记抗体。 在目标4中，我们将选择患者 这些患者用I-131抗体表现出良好的肿瘤摄取， 单次高剂量的I-131抗体 绕过骨髓 这种治疗的损害，患者将有骨髓储存之前， 接受治疗后再输注

This grant combines an integrated set of laboratory science and clinical investigations specifically focused on improving the ability to diagnostically image and potentially treat human cancer using radiolabeled monoclonal antibodies. In Aim 1 we will develop improved methods of antibody radioiodination using an iodinated tyramine-cellobiose (TCB) adduct, designed to produce increased retention of radioiodine in tumors. Labeling methods will be optimized for yields and preservation of immunoreactivity and products will be tested in tumor cell suspensions and in tumored mice. In Aim 2 we will attempt immunospecific lymphoscintigraphy of tumored nodes in patients with metastatic melanoma. We have demonstrated non-specific uptake of antibody in tumored nodes; this will be blocked with subcutaneous doses of cold irrelevant antibody prior to simultaneous injection of I-131 specific and I-125 non- specific antibody. After I-131 imaging excised nodes will be analyzed by counting and dual isotope autoradiography. In Aim 3 we will extend our work on antibody imaging of documented melanoma and eventually cancers of the lung and breast. Using diagnostic doses of I-131 labeled antibody we will carefully measure biodistribution and tumor labeling and make estimates of internal radiation absorbed doses. We will determine if the quality of imaging and tumor deposition of antibody radiolabeled by the para- iodophenyl and tyramine-cellobiose methods is improved compared to chloramine-T labeled antibody. In Aim 4 we will select patients who show good tumor uptake with I-131 antibody and treat them with single high doses of I-131 antibody. To circumvent bone marrow damage with this treatment, patients will have marrow stored prior to therapy and reinfused afterward.