Finstad C L, Lloyd K O, Federici M G, Divgi C, Venkatraman E, Barakat R R, Finn R D, Larson S M, Hoskins W J, Humm J L
Gynecology Service, Department of Surgery, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Clin Cancer Res. 1997 Aug;3(8):1433-42.
Our objective was to quantify the targeting of the monoclonal antibody (mAb) MX35 F(ab')2 to micrometastatic epithelial ovarian cancer. This mAb detects a Mr 95,000 glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. Six patients with minimal residual disease from an imaging trial were injected with 2 or 10 mg of 131I- and 125I-labeled mAb MX35 F(ab')2. Biopsied samples were removed at second-look laparotomy 1-5 days post-i.v. or -i.p. infusion of antibody. Serial cryostat sections were stained by indirect immunoperoxidase method for antigen distribution and exposed to storage phosphor screens for quantitative autoradiography. Coregistration of tumor histology, antigen expression, and radionuclide distribution demonstrated specific localization in micrometastatic tumor foci (50 micrometer to 1 mm) found within tissue stroma. The radiolabeled antibody uptake determined by well scintillation counts ranged between 5.2 and 223.5 x 10(-4) percentage of injected dose/g of tumor tissue for 131I. Specific localization of mAb in tumor was determined by tumor:normal tissue (fat) ratios ranging from 0.9:1 to 35.9:1 for 131I. The high resolution and linear response of the storage phosphor screen imager was used to estimate the radionuclide activity localized in each micrometastatic site. Quantitation of phosphor screen response revealed microCi/g values of 0.026-0.341 for normal tissue and 0.184-6.092 for tumor biopsies, evaluated 4 or 5 days post-antibody injection. The tumor:normal tissue (adjacent to tumor) ratios were between 1 and 4 times greater using the phosphor screen method than well counter measurements, but even larger variations of ratios up to 20:1 were observed between tumor cell foci and stromal cells within the same tissue section. This study has demonstrated that mAb MX35 F(ab')2 localizes to the micrometastatic ovarian carcinoma deposits within the peritoneal cavity. The dosimetry results suggest a therapeutic potential for this antibody in patients with minimal residual disease (<5 mm).
我们的目标是量化单克隆抗体（mAb）MX35 F(ab')2对微小转移上皮性卵巢癌的靶向性。该单克隆抗体可检测到一种分子量为95,000的糖蛋白，其在80%的卵巢肿瘤标本中呈均匀分布。对6例来自一项影像学试验的微小残留病患者注射2或10 mg的131I和125I标记的mAb MX35 F(ab')2。在静脉内或腹腔内输注抗体后1至5天进行二次剖腹探查时取出活检样本。连续冰冻切片通过间接免疫过氧化物酶法进行抗原分布染色，并暴露于储存磷光屏以进行定量放射自显影。肿瘤组织学、抗原表达和放射性核素分布的配准显示在组织基质内发现的微小转移瘤灶（50微米至1毫米）中有特异性定位。通过井型闪烁计数法测定的放射性标记抗体摄取量，对于131I而言，在每克肿瘤组织中为注射剂量的5.2至223.5×10(-4)%。通过肿瘤与正常组织（脂肪）的比值确定mAb在肿瘤中的特异性定位，对于131I而言，该比值范围为0.9:1至35.9:1。储存磷光屏成像仪的高分辨率和线性响应被用于估计每个微小转移部位的放射性核素活性。磷光屏响应的定量分析显示，在抗体注射后4或5天评估，正常组织的微居里/克值为0.026 - 0.341，肿瘤活检样本的微居里/克值为0.184 - 6.092。使用磷光屏方法得到的肿瘤与正常组织（与肿瘤相邻）的比值比井型计数器测量值大1至4倍，但在同一组织切片内的肿瘤细胞灶与基质细胞之间观察到的比值变化甚至更大，可达20:1。本研究表明，mAb MX35 F(ab')2定位于腹腔内的微小转移卵巢癌沉积物。剂量学结果表明该抗体对微小残留病（<5毫米）患者具有治疗潜力。
