Biodistribution of iodine-131-labled chimeric monoclonal antibody in patients following intratumoral administraion in advanced lung carcinoma
- VernacularTitle:~(131)碘肿瘤细胞核人鼠嵌合单抗肺癌内直接注射后体内的生物学分布
- Author:
Beilei LI
;
Shaoliang CHEN
;
Zhaoqiang XU
;
Like YU
;
Tian LI
;
Hongcheng SHI
- Publication Type:Journal Article
- Keywords:
chimeric monoclonal antibody (chTNT);
tumor;
radiation imaging;
radioimmunotherapy
- From:
Fudan University Journal of Medical Sciences
2009;36(4):475-478,489
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the biodistribution of intratumoral administerd~(131)Ⅰ-labeled human-mouse chimeric monoclonal antibody (chTNT) in patients with advanced lung carcinoma. Methods Eleven patients enrolled had cytological and histological confirmed diagnoses of either stage Ⅲ b or stage Ⅳ inoperable lung carcinoma. Intratumoral injection was directed by thoracic CT-guided catheter using a multi-holed needle. The dose for each patient was 18.5 - 37 MBq/cm~3 tumor mass. Blood samples were drawn at different time intervals for up to 13 days, and urine samples were collected for up to 11 days after injection for pharmacokinetic studies. In vivo stability was examined by HPLC by analyzing serum and urine, which were found to contain~(131)Ⅰ-chTNT. Whole body images were taken for quantitative organ and tumor biodistribution studies. Results In all 11 patients,~(131)Ⅰ-chTNT was the major component of the radiolabel in serum. Within 96 hours after administration, it was 100% stable. Plasma disappearance curves of ~(131)Ⅰ-chTNT were best fit by a two-exponential model in all patients with T_(1/2kα) of (0. 89±0. 17) h and T_(1/2β) of (86.88 ± 25.97)h. Free Ⅰ was the only metabolite of Ⅰ-chTNT that appeared in urine. A biodistribution study demonstrated excellent localization of the radioactivity in tumors. The accumulated radioactivity in urine at 264 h was (58.37 △Corresponding author E-mail:chen. shaoliang@zs-hospital. sh. cn±17.45) % of the injection dose. There was (51.05±8.41)%ID ,~(131)Ⅰ-chTNT in the tumor at 30 min after injection, and the tumor/lung (T/N) ratio was 63.87 ± 25.71. It remained (3.47 ± 3.27) %ID at 264 h,and the T/N ratio was 9. 61 ± 11.00. Among the main target organs, accumulation of the radiolabeled antibody was mainly found in lungs, liver, heart, kidneys, spleen and thyroid.Conclusions Pharmacokinietics of ~(131)Ⅰ-chTNT follows a two-exponential model. According to its long preservation in tumor tissue, intratumoral injection of~(131)Ⅰ-chTNT is good for tumor therapy.
