Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Australia.
J Nucl Med. 2021 Jun 1;62(6):787-794. doi: 10.2967/jnumed.120.253146. Epub 2021 Jan 28.
ABT-806 is a tumor-specific antibody targeting the epidermal growth factor receptor (EGFR). This study assessed safety, biodistribution, and pharmacokinetics of In-radiolabeled ABT-806 (ABT-806i) and effects of repeated doses of ABT-806 on receptor occupancy. Eligible patients had advanced tumors likely to express EGFR/EGFRvIII; adequate performance status and organ function; and measurable disease by RECIST 1.1. In cohort 1, 6 patients received a bolus administration of ABT-806i and underwent SPECT followed by whole-body planar scans. In cohort 2, 12 patients were imaged similarly as in 1 initially; thereafter, they received 3 doses of unlabeled ABT-806, before another dose of ABT-806i with associated SPECT and whole-body planar scans. At the end of both cohorts, patients who had stable or responding disease were able to enroll into an extension study (M12-326) in which they received unlabeled ABT-806 every 2 wk until disease progression, withdrawal of consent, or intolerable toxicity. No toxicity related to ABT-806i infusion was observed. ABT-806i showed minimal uptake in normal tissues and cleared gradually from blood with a half-life of 6.0 ± 1.5 d. The mean effective dose of ABT-806i was 0.137 mSv/MBq for males and 0.183 mSv/MBq for females. ABT-806i tumor uptake varied and did not correlate with archived tumor EGFR expression. No change in ABT-806i uptake was observed after interval ABT-806 treatment, indicating stable EGFR expression in tumor. The patient with highest tumor uptake of ABT-806i had advanced head and neck cancer and experienced a partial response. ABT-806i allows for real-time imaging of EGFR conformational expression in tumors, has an acceptable radiation dosimetry, and provides important additional information about antigen expression compared with standard approaches using archival tissue. Its role to assist in patient selection for EGFR-based therapeutics and investigate treatment resistance should be further investigated.
ABT-806 是一种针对表皮生长因子受体 (EGFR) 的肿瘤特异性抗体。本研究评估了 In-放射性标记的 ABT-806（ABT-806i）的安全性、生物分布和药代动力学，以及重复给予 ABT-806 对受体占有率的影响。符合条件的患者具有可能表达 EGFR/EGFRvIII 的晚期肿瘤；有足够的功能状态和器官功能；并且根据 RECIST 1.1 标准可测量疾病。在队列 1 中，6 名患者接受 ABT-806i 的推注给药，并进行 SPECT 后行全身平面扫描。在队列 2 中，12 名患者最初以与 1 相同的方式进行成像；此后，他们接受了 3 剂未标记的 ABT-806，然后再给予 ABT-806i 并进行相关的 SPECT 和全身平面扫描。在两个队列结束时，稳定或有反应的疾病患者能够参加一项扩展研究（M12-326），在该研究中，他们每 2 周接受一次未标记的 ABT-806，直到疾病进展、撤回同意或无法耐受毒性。未观察到与 ABT-806i 输注相关的毒性。ABT-806i 在正常组织中的摄取很少，在血液中的半衰期为 6.0±1.5 d，逐渐清除。ABT-806i 的平均有效剂量男性为 0.137 mSv/MBq，女性为 0.183 mSv/MBq。ABT-806i 肿瘤摄取量不同，与存档肿瘤 EGFR 表达无关。间隔 ABT-806 治疗后未观察到 ABT-806i 摄取量的变化，表明肿瘤 EGFR 表达稳定。ABT-806i 摄取量最高的患者患有晚期头颈部癌症，部分缓解。ABT-806i 允许实时成像肿瘤中 EGFR 构象表达，具有可接受的辐射剂量学，并与使用存档组织的标准方法相比提供了关于抗原表达的重要补充信息。应进一步研究其在协助患者选择 EGFR 为基础的治疗和研究治疗耐药性方面的作用。
