Rubin S C, Kostakoglu L, Divgi C, Federici M G, Finstad C L, Lloyd K O, Larson S M, Hoskins W J
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Gynecol Oncol. 1993 Oct;51(1):61-6. doi: 10.1006/gyno.1993.1247.
Murine monoclonal antibody (MAb) MX 35 shows strong homogeneous reactivity with more than 90% of epithelial ovarian cancers. Twenty-five patients with advanced ovarian cancer were entered into a clinical trial using 125I- or 131I-labeled MX 35 in doses of 2, 10, or 20 mg administered by intravenous (i.v.) or intraperitoneal injection. All patients underwent laparotomy at 7 to 20 days following MAb injection to assess tumor distribution, obtain biopsies of tumor and normal tissue, and evaluate the use of an intraoperative hand-held gamma-detecting device. Following i.v. injection, serum Mab half-life was 36 hr. Tumor biopsies obtained at surgery showed MAb accumulation of from 6.7 x 10(-3) to 4.0 x 10(-5)% injected dose/g of tissue. There was no correlation between absolute MAb accumulation in tumor and MAb dose administered. Regression analysis showed a correlation between MAb accumulation and the interval between MAb injection and surgery (P = 0.008). Specific localization of MAb in tumor was demonstrated by tumor:normal tissue ratios ranging from 2.3:1 to 34:1 (mean, 10.18:1). The tumor:normal tissue ratios were not significantly related to MAb dose, the level of immunohistochemical antigen expression, or the interval between MAb injection and surgery. Due to the relatively long serum half-life, mean tumor:serum ratios were only 1.53 following IV injection. This ratio did not correlate with MAb dose, days from injection, or antigen expression. There was an excellent correlation (P = 0.001) between MAb uptake, as measured by the intraoperative hand-held gamma counter, and direct gamma counting of excised tissues. MAb MX 35 localizes well to tumor in selected patients with ovarian cancer, and MAb uptake can be reliably quantitated in vivo with the hand-held intraoperative gamma counter.
鼠单克隆抗体（MAb）MX 35与90%以上的上皮性卵巢癌呈现出强烈的均一反应性。25例晚期卵巢癌患者进入一项临床试验，使用静脉注射（i.v.）或腹腔注射剂量为2、10或20mg的125I或131I标记的MX 35。所有患者在注射单克隆抗体后7至20天接受剖腹手术，以评估肿瘤分布、获取肿瘤和正常组织的活检样本，并评估术中手持式γ探测装置的使用情况。静脉注射后，血清单克隆抗体半衰期为36小时。手术时获取的肿瘤活检样本显示，单克隆抗体在组织中的积累量为注射剂量的6.7×10⁻³%至4.0×10⁻⁵%/g。肿瘤中绝对单克隆抗体积累量与所给单克隆抗体剂量之间无相关性。回归分析表明，单克隆抗体积累量与单克隆抗体注射和手术之间的间隔时间相关（P = 0.008）。肿瘤与正常组织的单克隆抗体特异性定位通过肿瘤与正常组织的比例为2.3:1至34:1（平均为10.18:1）得以证明。肿瘤与正常组织的比例与单克隆抗体剂量、免疫组化抗原表达水平或单克隆抗体注射与手术之间的间隔时间无显著相关性。由于血清半衰期相对较长，静脉注射后平均肿瘤与血清比例仅为1.53。该比例与单克隆抗体剂量、注射后天数或抗原表达无关。通过术中手持式γ计数器测量的单克隆抗体摄取量与切除组织的直接γ计数之间存在极好的相关性（P = 0.001）。单克隆抗体MX 35在部分卵巢癌患者的肿瘤中定位良好，并且可以使用术中手持式γ计数器在体内可靠地定量单克隆抗体摄取量。
