背景:用锆-89标记的[89Zr]Zr-DFO-girentuximab进行PET/CT成像,靶向肿瘤抗原CAIX,可能有助于透明细胞肾细胞癌(RCC)和其他肾脏和肾外病变的分化和表征,并已在欧洲和美国队列中进行了研究。我们报告了评估安全性的第一阶段研究的结果,生物分布,[89Zr]Zr-DFO-girentuximab在日本疑似肾癌患者中的剂量测定。
方法:符合条件的成年患者接受37MBq(±10%;10mg质量剂量)静脉注射[89Zr]Zr-DFO-girentuximab。根据不良事件评估安全性和耐受性,合并用药,体检,生命体征,血液学,血清化学,尿液分析,人抗嵌合抗体测量,和预定间隔的12导联心电图。在给药后0.5、4、24、72小时和第5天±2天获得的PET/CT图像评估生物分布和正常器官和肿瘤剂量测定。
结果:[89Zr]Zr-DFO-girentuximab按照方案对6例患者进行给药。未报告因治疗引起的不良事件。剂量学分析表明放射性在体内广泛分布,健康器官的吸收剂量在肝脏中最高(平均值±标准偏差)(1.365±0.245mGy/MBq),肾脏(1.126±0.190mGy/MBq),心壁(1.096±0.232mGy/MBq),和脾脏(1.072±0.466mGy/MBq)。平均有效剂量,根据所施用的放射性剂量进行调整,为0.470mSv/MBq。辐射剂量在目标肿瘤中高度积累,而其他器官没有任何异常积累的报道。
结论:本研究表明,[89Zr]Zr-DFO-girentuximab对日本疑似RCC患者具有良好的安全性,耐受性良好,与先前研究的人群具有相似的剂量学特征。
BACKGROUND: PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I
study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC.
METHODS: Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration.
RESULTS: [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported.
CONCLUSIONS: This
study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.