Hopkins K, Chandler C, Bullimore J, Sandeman D, Coakham H, Kemshead J T
Imperial Cancer Research Fund, Frenchay Hospital, Bristol, UK.
Radiother Oncol. 1995 Feb;34(2):121-31. doi: 10.1016/0167-8140(95)01514-h.
A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 (90Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved.
一项关于通过向复发恶性胶质瘤患者肿瘤内直接注射钇-90(90Y)放射性免疫缀合物进行治疗的初步研究已完成。患者在进行最大程度的肿瘤切除后被招募,并接受1至3次与名为ERIC-1的单克隆抗体结合的90Y注射,该抗体可结合神经细胞黏附分子。收集数据以确定临床毒性、药代动力学以及对腔壁和关键身体器官的辐射剂量。15名患者共完成了23次注射,平均注射活度为675 MBq(范围为399 - 921)。早期毒性表现为脑水肿,用地塞米松可轻松控制。观察到有延迟性骨髓抑制,但无需干预。药代动力学分析证实同位素在腔内的保留时间延长,而血液中的活性相应较低。使用医学内照射剂量学(MIRD)方案将这些数据转化为吸收辐射剂量的估计值。与正常组织剂量相比,腔壁即“肿瘤”的平均剂量和剂量率非常高,如果实现了靶向则更具优势。