Riva P, Arista A, Tison V, Sturiale C, Franceschi G, Spinelli A, Riva N, Casi M, Moscatelli G, Frattarelli M
Nuclear Medicine Department, Istituto Oncologico Romagnolo, M. Bufalini Hospital, Cesena, Italy.
Cancer. 1994 Feb 1;73(3 Suppl):1076-82. doi: 10.1002/1097-0142(19940201)73:3+<1076::aid-cncr2820731347>3.0.co;2-z.
Intralesional radioimmunotherapy (RAIT) may improve the management of malignant gliomas whose prognosis is, at present, very poor. Current treatment modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival by a few months but cannot prevent tumor recurrence.
Following one or more surgical operations, radiotherapy, and chemotherapy, 24 patients with recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2 murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN). This antigen is expressed in large amounts in the stroma of glial tumors but not normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled antibodies were injected directly into the tumor by means of a removable catheter or an indwelling catheter placed in the site of disease at the time of craniotomy. The patients were admitted to the protocol if histochemical analysis of their tumors demonstrated the presence of TN in high abundance. Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37 MBq 131I) were studied. RAIT was performed by the administration of escalating doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was repeated two, three, or four times (on 8, 3 and 4 patients, respectively).
Pharmacokinetic data resulted, on average, as follows: the 24-hour tumor/background ratio was 16.6; the percentage of injected dose concentrated per gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per MBq of 131I injected. Both systemic and brain toxicities were absent, while human anti-mouse antibody production after MoAb administration occurred in only a few cases. At present, 17 patients are assessable, with a median survival time of 16 months. Objective responses consisted of 5 tumor stabilizations (median time, 9 months), 3 partial remissions (11 months), and 3 complete remissions (15 months).
瘤内放射免疫疗法（RAIT）可能改善恶性胶质瘤的治疗，目前其预后非常差。当前的治疗方式（如手术、放疗和化疗）可能使生存期延长几个月，但无法预防肿瘤复发。
在接受一次或多次手术、放疗和化疗后，24例复发性恶性胶质瘤患者（23例脑部肿瘤和1例脊髓肿瘤）接受了用两种抗腱生蛋白（TN）的鼠单克隆抗体（MoAb）BC - 2和BC - 4进行的RAIT治疗。这种抗原在胶质肿瘤的基质中大量表达，但在正常脑组织中不表达。使用的同位素是碘 - 131（¹³¹I）。放射性标记抗体通过可移除导管或在开颅手术时置于病变部位的留置导管直接注入肿瘤。如果对患者肿瘤的组织化学分析显示大量存在TN，则将其纳入该方案。研究了瘤内示踪剂剂量（1mg MoAb和37MBq ¹³¹I）的生物分布和剂量测定。RAIT通过给予递增剂量的放射性碘进行，剂量范围从15mCi到57mCi。在许多情况下，RAIT重复进行了2次、3次或4次（分别针对8例、3例和4例患者）。
药代动力学数据平均如下：24小时肿瘤/本底比值为16.6；24小时每克肿瘤中浓集的注射剂量百分比为2.4%；MoAb在肿瘤处的有效半衰期为74.5小时。每注入1MBq ¹³¹I对肿瘤的平均辐射剂量为36.48cGy。既无全身毒性也无脑部毒性，而在给予MoAb后仅少数病例出现人抗鼠抗体产生。目前，17例患者可进行评估，中位生存期为16个月。客观反应包括5例肿瘤稳定（中位时间9个月）、3例部分缓解（11个月）和3例完全缓解（15个月）。
