Steffens M G, Boerman O C, Oosterwijk-Wakka J C, Oosterhof G O, Witjes J A, Koenders E B, Oyen W J, Buijs W C, Debruyne F M, Corstens F H, Oosterwijk E
Department of Urology, University Hospital Nijmegen, The Netherlands.
J Clin Oncol. 1997 Apr;15(4):1529-37. doi: 10.1200/JCO.1997.15.4.1529.
Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody.
Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed.
In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients.
131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.
研究碘131（¹³¹I）标记的嵌合单克隆抗体（mAb）G250（cG250）在肾细胞癌（RCC）患者中的药代动力学、生物分布、免疫原性及成像特征，以确定该抗体的治疗潜力。
16例RCC患者接受单次静脉注射6 mCi的¹³¹I标记cG250。研究了5种蛋白剂量水平（2至50 mg）。采集平面闪烁图像，并在注射后7天手术时获取正常组织活检和肿瘤样本。使用夹心酶联免疫吸附测定（ELISA）研究cG250的免疫原性，并进行剂量学分析。
在所有抗原阳性肿瘤患者（n = 13）中，原发肿瘤和所有已知转移灶均清晰可见。原发肿瘤的总摄取量以注射剂量的百分比（%ID）表示，范围为2.4至9.0。局部观察到¹³¹I-cG250摄取高达0.52% ID/g。然而，肿瘤内摄取高度不均一。¹³¹I-cG250在非肿瘤组织中的摄取仍然较低。剂量学分析表明，原发肿瘤接受的剂量高达0.48 Gy/mCi。这些肿瘤内选定的“热点区域”接受的剂量高达0.72 Gy/mCi。一处骨转移灶接受0.23 Gy/mCi，区域淋巴结转移灶接受0.20 Gy/mCi。16例患者中有2例检测到极低水平的人抗嵌合抗体（HACA）。
¹³¹I-cG250在肿瘤中的摄取是实体瘤抗肿瘤抗体临床研究中报道的最高水平之一。由于当给予高剂量¹³¹I-cG250（> 100 mCi）时可能将肿瘤杀灭剂量导向肿瘤，且cG250似乎无免疫原性，因此cG250是RCC放射免疫治疗的一种有前景的载体。
