Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration
Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration
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DOI：
10.1007/s002590050335
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发表时间：
1998-11-01
期刊：
影响因子：
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通讯作者：
Corstens, FHM
中科院分区：
文献类型：
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作者：
Buijs, WCAM;Tibben, JG;Corstens, FHM
本研究确定了嵌合碘-131标记的MOv18 Ige在放射免疫治疗中的腹腔注射和静脉注射的潜力。在患者中研究了cMOv18 IgG两种给药途径的相关剂量学。8例疑似卵巢癌患者接受150 MBq I-131-cMOv18 IgG免疫检测，采集血样和尿液，并采集连续伽马相机图像。另一组4例患者接受7.5 MBq I-131-cMOv18 IgG静脉注射。所有患者均在手术时进行组织活检。给药后血中活性用双指数曲线描述，平均摄取和消除半衰期分别为6.9+/-3.2 h和160+/-45 h。静脉输注时，消除期的平均半衰期为103+/-12小时。在96小时内，单药和静脉给药的累积尿排泄量分别为17%+/-3% LD和21%+/-7% ID。服用i.p.后的显像显示卵巢癌病变中积聚，而其他组织的活性随时间而下降。在卵巢癌组织标本中测定的肿瘤摄取范围为口服给药3.4%至12.3% ID/kg，静脉给药3.6%至5.4% ID/kg。剂量学分析数据显示，分别经内服和静脉给药后，1.7-4.3 mGy/MBq和1.7-2.2 mGy/MBq可引导至实体细胞或腹水细胞。假设2 Gy的骨髓吸收剂量为剂量极限，则可通过口服途径安全给药的I-131- cMOv18 IgG总活性为4.1 GBq，通过静脉注射途径可安全给药的总活性为3.5 GBq。在这一最大耐受剂量下，腹腔和静脉给药后可分别达到18 Gy和8 Gy对腹腔1 g肿瘤的最大吸收剂量。对于腹腔给药途径，当考虑到腹膜活动的电子剂量时，对肿瘤的剂量估计甚至更高：30 Gy和22 Gy的肿瘤总剂量将分别在肿瘤表面和0.2 mm深度被吸收。综上所述，I-131- cMOv18 IgG可用于无正常器官毒性的腹腔卵巢癌病变患者的肿瘤治疗剂量。口服给药似乎比静脉给药更可取。
In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 Ige for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq I-131-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq I-131-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% LD and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while ail other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p, administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p, and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq I-131- cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i.p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with I-131- cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v, administration.