Juweid M, Sharkey R M, Behr T, Swayne L C, Rubin A D, Hanley D, Herskovic T, Markowitz A, Siegel J, Goldenberg D M
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Newark, New Jersey 07103, USA.
Cancer Res. 1995 Dec 1;55(23 Suppl):5946s-5951s.
The targeting potential of 131I-labeled NP-4 and MN-14 anti-CEA (carcinoembryonic antigen) monoclonal antibodies (MAbs) was assessed in 19 patients with metastatic medullary thyroid cancer (MTC). Seventeen of these patients also entered pilot radioimmunotherapy studies with nonmyeloablative doses of 131I-anti-CEA MAbs. Tumor targeting was possible in all 19 patients, with an overall lesion sensitivity of 91%. Tumor dosimetry with 131I-MN-14 IgG or F(ab)2 was very favorable, with tumor doses of 14.3 +/- 8.3 cGy/mCi and tumor:red marrow dose ratios exceeding 3:1 for most lesions. Limited antitumor effects lasting up to 26+ months, based on physical exam, tumor markers, computed tomography, or a followup MAb scan, were seen in 5 of 11 assessable patients given relatively low doses of 131I-labeled anti-CEA MAbs. We conclude that anti-CEA MAbs are excellent agents for targeting metastatic MTC. The high tumor uptake of the 131I-anti-CEA antibodies and evidence of tumor response in some patients suggest that radioimmunotherapy with radioiodinated anti-CEA MAbs may be an effective treatment for MTC, particularly when the maximum tolerated dose is given alone or in combination with autologous red marrow or peripheral stem cell support.
在19例转移性甲状腺髓样癌（MTC）患者中评估了131I标记的NP - 4和MN - 14抗癌胚抗原（CEA）单克隆抗体（MAb）的靶向潜力。其中17例患者还进入了非清髓剂量131I抗CEA MAb的放射免疫治疗试点研究。所有19例患者均实现肿瘤靶向，总体病灶敏感性为91%。131I - MN - 14 IgG或F(ab)2的肿瘤剂量测定结果非常理想，大多数病灶的肿瘤剂量为14.3±8.3 cGy/mCi，肿瘤与红骨髓剂量比超过3:1。在给予相对低剂量131I标记抗CEA MAb的11例可评估患者中，5例患者基于体格检查、肿瘤标志物、计算机断层扫描或后续MAb扫描观察到持续长达26个月以上的有限抗肿瘤效果。我们得出结论，抗CEA MAb是靶向转移性MTC的优秀药物。131I抗CEA抗体的高肿瘤摄取以及部分患者的肿瘤反应证据表明，放射性碘标记抗CEA MAb的放射免疫治疗可能是MTC的有效治疗方法，特别是当单独给予最大耐受剂量或与自体红骨髓或外周干细胞支持联合使用时。
