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通过膀胱内灌注铜-67标记的抗MUC1粘蛋白单克隆抗体C595靶向治疗浅表性膀胱癌。

Targeting superficial bladder cancer by the intravesical administration of copper-67-labeled anti-MUC1 mucin monoclonal antibody C595.

作者信息

Hughes O D, Bishop M C, Perkins A C, Wastie M L, Denton G, Price M R, Frier M, Denley H, Rutherford R, Schubiger P A

机构信息

Departments of Urology and Pathology, City Hospital, Nottingham, United Kingdom.

出版信息

J Clin Oncol. 2000 Jan;18(2):363-70. doi: 10.1200/JCO.2000.18.2.363.

Abstract

PURPOSE

More effective intravesical agents are required to limit the recurrence and progression of superficial bladder cancer. This study assessed the ability of copper-67 ((67)Cu)-C595 murine antimucin monoclonal antibody to bind selectively to superficial bladder tumors when administered intravesically, with a view to its development for therapy.

PATIENTS AND METHODS

Approximately 20 MBq of (67)Cu-C595 monoclonal antibody was administered intravesically to 16 patients with a clinical indication of superficial bladder cancer. After 1 hour, the bladder was drained and irrigated. Tissue uptake was assessed by imaging and by the assay of tumor and normal tissues obtained by endoscopic resection.

RESULTS

Tumor was correctly identified in the images of 12 of 15 patients who were subsequently found to have tumors. Assay of biopsy samples at 2 hours showed a mean tumor uptake of 59.4% of the injected dose per kilogram (SD = 48.0), with a tumor-to-normal tissue ratio of 14.6:1 (SD = 20). After 24 hours (n = 5), this decreased to 4.3% of the injected dose per kilogram (SD = 2.9), with a tumor-to-normal tissue ratio of 1.8:1 (SD = 0.8).

CONCLUSION

This study indicates a promising method for the treatment of superficial bladder cancer. Although the mean initial tumor uptake was high, effective therapy of bladder tumors will require an increased retention of the cytotoxic radionuclide in tumor tissue.

摘要

目的

需要更有效的膀胱内给药制剂来限制浅表性膀胱癌的复发和进展。本研究评估了铜-67(67Cu)-C595鼠抗粘蛋白单克隆抗体膀胱内给药时选择性结合浅表性膀胱肿瘤的能力,以期将其开发用于治疗。

患者和方法

向16例有浅表性膀胱癌临床指征的患者膀胱内给予约20MBq的67Cu-C595单克隆抗体。1小时后,排空膀胱并进行冲洗。通过成像以及对经内镜切除获得的肿瘤和正常组织进行检测来评估组织摄取情况。

结果

在随后被发现患有肿瘤的15例患者中,有12例的图像中正确识别出了肿瘤。2小时时活检样本检测显示,肿瘤平均摄取量为每千克注射剂量的59.4%(标准差=48.0),肿瘤与正常组织的比值为14.6:1(标准差=20)。24小时后(n=5),该值降至每千克注射剂量的4.3%(标准差=2.9),肿瘤与正常组织的比值为1.8:1(标准差=0.8)。

结论

本研究表明了一种治疗浅表性膀胱癌的有前景的方法。虽然初始肿瘤平均摄取量较高,但要有效治疗膀胱肿瘤,需要增加细胞毒性放射性核素在肿瘤组织中的滞留量。

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