Development of technetium-99m and rhenium-186 labeled monoclonal antibodies for imaging and therapy.

为探讨~（99）Tc和~（186）Tc标记的抗癌胚抗原（CEA）单克隆抗体的显像和治疗方法，对12例结直肠癌患者静脉注射~（99）Tc标记的CEA单克隆抗体，观察其生物分布和肿瘤摄取。11例（92%）显示抗体阳性结果，SPECT获得的肿瘤与正常组织的比值与手术标本获得的结果相关性良好。肿瘤与正常组织的比例最高达到14以上，有几例似乎是放射免疫治疗的良好候选者。7例卵巢癌组织中有3例有99 m标记的抗CA 125抗体积聚，有待进一步研究。单克隆抗体临床应用的最大问题是在接受单克隆抗体治疗的患者血清中产生人抗鼠抗体（HAMA）。基因技术的快速发展使我们能够生产人源化的单克隆抗体。将锝-99m标记的人源化抗体安全地给予患者，并且在其血清中未检测到HAMA。人源化抗体的临床应用不仅在免疫闪烁显像方面，而且在肿瘤治疗方面也有很大的前景。

This study was performed to develop new imaging and therapeutic methods using technetium-99m and rhenium-186 labeled monoclonal antibodies.Technetium-99m labeled antibodies against carcinoembryonic antigen (CEA) were intravenously administered to patients with colorectal cancer, and its biodistribution and tumor uptake were examined in 12 patients. Eleven (92%) cases showed positive results with antibodies and tumor-to-normal tissue ratios obtained with SPECT correlated well with those obtained using surgical specimen. The highest tumor-to-normal tissue ratio reached more than 14 and there were several cases who seemed to be good candidates for radioimmunotherapy. Techetium-99m labeled anti-CA125 antibodies also accumulated in the ovarian cancer tissues in 3 out of 7 cases and needs further investigation.The biggest problem inherent to clinical use of monoclonal antibodies is the generation of human anti-murine antibody (HAMA) in the serum of patients who received monoclonal antibodies. Rapid progress of gene technology allowed us to produced humanized monoclonal antibodies. Technetium-99m labeled humanized antibodies were safely administered to patients and no HAMA were detectable in their serum. Clinical use of humanized antibodies seemed promising not only in the immunoscintigraphy but also in the therapy of cancer.