目的 研究肺癌瘤内直接注射~(131)Ⅰ-chTNT后患者体内分布状况.方法 经病理组织学确诊的原发性肺癌患者11例.根据CT定位,单次瘤内直接注射~(131)Ⅰ-chTNT 18.5～37 MBq/cm~3后,多时点测量血、尿放射性.应用HPLC法检测~(131)Ⅰ-chTNT在体内的稳定性和代谢情况.采用连续显像法估算全身、各主要脏器和肿瘤的放射性,并转换为注射剂量百分率(%ID),以观察~(131)Ⅰ-chTNT在体内的分布.结果 所有11例患者HPLC榆测结果显示,注射后24、48、72、96 h内血清中~(131)Ⅰ-chTNT均以原形存在,原形含量达100%.经计算机拟合,血清药-时曲线符合静脉外给药二室模型,T_(t/2kα)(0.89±0.17)h,T~(131)(1/2β)(86.88±25.97)h.游离~(131)Ⅰ是尿内~(131)Ⅰ-chTNT的唯一代谢产物.264 h累计尿排泄量为注射量的(58.37±17.45)%.瘤内给药后30 min,瘤内~(131)Ⅰ-chTNT量为(51.05±8.41)%ID,瘤/肺比值(T/N)高达(63.87±25.71).264 h时瘤内~(131)Ⅰ-chTNT残留(3.47±3.27)%ID,T/N为(9.61±11.00).全身主要器官中,放射性主要集中在肺、肝、心、肾、脾和甲状腺中.结论 ~(131)Ⅰ-chTNT瘤内直接注射后在瘤内停留时间较长,有利于肿瘤治疗.%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.
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