Wärnberg Fredrik, Axelsson Oskar, Curiac Dan, Hargreaves Paul, Karakatsanis Andreas, Lekmeechai Sujinna, Hansen Mats
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden (F.W.); Spago Nanomedical AB, Lund, Sweden (O.A., P.H., S.L., M.H.); CTC Gothia Forum, Sahlgrenska University Hospital, Göteborg, Sweden (D.C.); and Uppsala Universitet, Institutionen för Kirurgiska Vetenskaper, Endokrinkirurgi, Uppsala, Sweden (A.K.).
Invest Radiol. 2025 Sep 1;60(9):577-585. doi: 10.1097/RLI.0000000000001164.
The primary objective of the first-in-human (FIH) study was to evaluate the safety and tolerability of the manganese (Mn)-based contrast agent pegfosimer manganese in participants with newly diagnosed breast cancer, and secondary objectives included preliminary efficacy, and pharmacokinetics (PK) of the agent.
A single intravenous 1-hour infusion of pegfosimer manganese was administered to 2 cohorts; 6 participants at the starting dose of 10 μmol Mn/kg, followed by 8 participants at the expansion dose of 20 μmol Mn/kg, cohorts 1 and 2, respectively. The safety was evaluated based on reported adverse events (AEs), including serious AEs, physical examination, vital signs, electrocardiogram, and safety laboratory parameters. Magnetic resonance imaging (MRI) acquisition was performed precontrast and postcontrast to assess the clinical relevance of images in primary breast tumors, liver, and pancreas relative to reference tissue. PK parameters were calculated from a noncompartmental analysis of the plasma Mn concentrations versus time.
There was a total of 29 AEs reported to all participants of the 2 cohorts. The AEs were mostly of mild to moderate severity and possibly or probably related to the contrast agent. No clinically significant changes in the safety laboratory parameters were reported, except for transiently elevated transaminases observed at the end of the infusion. Clinically relevant low-background MRI scans for clinical visualization of primary breast tumor, liver, and pancreas were obtained at the expanded dose level. Pegfosimer manganese has an initial plasma half-life of approximately 7 minutes.
The FIH study of pegfosimer manganese demonstrated an acceptable safety profile and sufficient contrast enhancement for clinically relevant MRI sequences in participants with primary breast tumors.
首次人体（FIH）研究的主要目的是评估基于锰（Mn）的造影剂聚乙二醇化磷酰肌醇锰对新诊断乳腺癌患者的安全性和耐受性，次要目的包括该药物的初步疗效和药代动力学（PK）。
对2个队列的患者进行单次静脉输注1小时的聚乙二醇化磷酰肌醇锰；队列1的6名参与者起始剂量为10 μmol Mn/kg，随后队列2的8名参与者扩展剂量为20 μmol Mn/kg。根据报告的不良事件（AE）评估安全性，包括严重不良事件、体格检查、生命体征、心电图和安全实验室参数。在注射造影剂前和注射后进行磁共振成像（MRI）采集，以评估原发性乳腺肿瘤、肝脏和胰腺相对于参考组织的图像临床相关性。通过对血浆锰浓度与时间的非房室分析计算PK参数。
2个队列的所有参与者共报告了29起不良事件。不良事件大多为轻度至中度严重程度，可能或很可能与造影剂有关。除输注结束时观察到转氨酶短暂升高外，未报告安全实验室参数有临床显著变化。在扩展剂量水平获得了用于原发性乳腺肿瘤、肝脏和胰腺临床可视化的临床相关低背景MRI扫描。聚乙二醇化磷酰肌醇锰的初始血浆半衰期约为7分钟。
聚乙二醇化磷酰肌醇锰的首次人体研究表明，对于原发性乳腺肿瘤患者，其安全性可接受，且在临床相关的MRI序列中具有足够的对比增强效果。
