PURPOSE PGN650 is a F(ab')2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. METHODS Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124I-PGN650 intravenously and underwent positron emission tomography-computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). RESULTS Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. CONCLUSION Although 124I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies.

中文翻译：

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124I-PGN650的首次人体评估：用于检测磷脂酰丝氨酸作为固体肿瘤微环境生物标志物的PET示踪剂。

用途PGN650是一种靶向磷脂酰丝氨酸（PS）的F（ab'）2抗体片段，磷脂酰丝氨酸（PS）通常不存在，响应于氧化应激而暴露于肿瘤细胞和肿瘤脉管上，并随着治疗而增加。将PGN650标记为124I，以创建正电子发射断层扫描（PET）剂，作为肿瘤微环境和对治疗反应的体内生物标记。在此0期研究中，我们评估了该示踪剂在一组癌症患者中的药代动力学，安全性，放射剂量学和靶向肿瘤。方法11名患有已知实体瘤的患者经静脉注射约140 MBq（3.8 mCi）124I-PGN650，并分别于1小时，3小时左右接受正电子发射断层扫描计算机断层扫描（PET / CT），然后在24小时或48小时后建立示踪动力学，以计算辐射剂量法（使用成年男性和女性模型对器官时间活动曲线和OLINDA / EXM进行积分）。结果已知的肿瘤灶显示出轻度增加的摄取，在最近的成像时间具有最高的活性。没有意外的不良事件。肝脏是接受最高辐射剂量（0.77 mGy / MBq）的器官。有效剂量为0.41 mSv / MBq。结论尽管124I-PGN650对于人类PET成像是安全的，但是使用这种药物治疗患者的肿瘤比以前在动物研究中观察到的少。结果已知的肿瘤灶显示出轻度增加的摄取，在最近的成像时间具有最高的活性。没有意外的不良事件。肝脏是接受最高辐射剂量（0.77 mGy / MBq）的器官。有效剂量为0.41 mSv / MBq。结论尽管124I-PGN650对于人类PET成像是安全的，但是使用这种药物治疗患者的肿瘤比以前在动物研究中观察到的少。结果已知的肿瘤灶显示出轻度增加的摄取，在最近的成像时间具有最高的活性。没有意外的不良事件。肝脏是接受最高辐射剂量（0.77 mGy / MBq）的器官。有效剂量为0.41 mSv / MBq。结论尽管124I-PGN650对于人类PET成像是安全的，但是使用这种药物治疗患者的肿瘤比以前在动物研究中观察到的少。