新诊断恶性胶质瘤患者中131I标记抗腱生蛋白81C6鼠单克隆抗体的剂量测定与影像学分析：一项II期研究

Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.

作者信息

Akabani Gamal, Reardon David A, Coleman R Edward, Wong Terence Z, Metzler Scott D, Bowsher James E, Barboriak Daniel P, Provenzale James M, Greer Kim L, DeLong David, Friedman Henry S, Friedman Allan H, Zhao Xiao-Guang, Pegram Charles N, McLendon Roger E, Bigner Darell D, Zalutsky Michael R

机构信息

Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

J Nucl Med. 2005 Jun;46(6):1042-51.

PMID:15937318

Abstract

UNLABELLED

The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy.

METHODS

Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients.

RESULTS

This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival.

CONCLUSION

This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

摘要

未标注

目的是对新诊断的恶性脑肿瘤患者进行剂量测定，并评估剂量反应关系。这些患者接受了将（131）I标记的抗腱生蛋白鼠源81C6单克隆抗体（mAb）直接注射到手术创建的切除腔（SCRC）中，随后进行常规外照射放疗和化疗。

方法

对33例原发性脑肿瘤患者，估计从切除腔界面边缘测量的2厘米厚壳层的吸收剂量。MRI/SPECT配准用于评估放射性标记的mAb在脑实质中的分布。对15例患者活检结果分类为肿瘤、放射性坏死或肿瘤与放射性坏死，并将这些结果与吸收剂量和剂量率相关联。此外，MRI/PET配准用于评估患者的影像学进展。

结果

该治疗策略使所有患者和多形性胶质母细胞瘤（GBM）患者的中位生存期分别为86周和79周。（131）I-μ81C6 mAb在SCRC中的平均停留时间为76小时（范围34 - 169小时）。所有患者2厘米腔边缘的平均吸收剂量为48 Gy（范围25 - 116 Gy），GBM患者为51 Gy（范围27 - 116 Gy）。在MRI/SPECT配准中，我们观察到（131）I-μ81C6 mAb在血管源性水肿区域有优先分布。对吸收剂量和剂量率与首次活检结果之间关系的分析得出最有利的吸收剂量为44 Gy。注意到生存期缩短与不可逆神经毒性之间存在相关性。与先前的近距离放射治疗临床研究进行了中位生存期的比较分析，结果显示平均增敏吸收剂量与中位生存期之间存在比例关系。