Gnesin Silvano, Müller Joachim, Burger Irene A, Meisel Alexander, Siano Marco, Früh Martin, Choschzick Matthias, Müller Cristina, Schibli Roger, Ametamey Simon M, Kaufmann Philipp A, Treyer Valerie, Prior John O, Schaefer Niklaus
Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Department of Radiology and Nuclear Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
EJNMMI Res. 2020 Apr 8;10(1):32. doi: 10.1186/s13550-020-00624-2.
The folate receptor alpha (FRα) is an interesting target for imaging and therapy of different cancers. We present the first in-human radiation dosimetry and radiation safety results acquired within a prospective, multicentric trial (NCT03242993) evaluating the F-AzaFol (3'-aza-2'-[F]fluorofolic acid) as the first clinically assessed PET tracer targeting the FRα.
Six eligible patients presented a histologically confirmed adenocarcinoma of the lung with measurable lesions (≥ 10 mm according to RECIST 1.1). TOF-PET images were acquired at 3, 11, 18, 30, 40, 50, and 60 min after the intravenous injection of 327 MBq (range 299-399 MBq) of F-AzaFol to establish dosimetry. Organ absorbed doses (AD), tumor AD, and patient effective doses (E) were assessed using the OLINDA/EXM v.2.0 software and compared with pre-clinical results.
No serious related adverse events were observed. The highest AD were in the liver, the kidneys, the urinary bladder, and the spleen (51.9, 45.8, 39.1, and 35.4 μGy/MBq, respectively). Estimated patient and gender-averaged E were 18.0 ± 2.6 and 19.7 ± 1.4 μSv/MBq, respectively. E in-human exceeded the value of 14.0 μSv/MBq extrapolated from pre-clinical data. Average tumor AD was 34.8 μGy/MBq (range 13.6-60.5 μGy/MBq).
F-Azafol is a PET agent with favorable dosimetric properties and a reasonable radiation dose burden for patients which merits further evaluation to assess its performance.
ClinicalTrial.gov, NCT03242993, posted on August 8, 2017.
叶酸受体α（FRα）是不同癌症成像和治疗的一个有趣靶点。我们展示了在前瞻性多中心试验（NCT03242993）中获得的首例人体辐射剂量测定和辐射安全结果，该试验评估了F - AzaFol（3'-氮杂-2'-[F]氟叶酸）作为首个临床评估的靶向FRα的PET示踪剂。
6名符合条件的患者患有经组织学证实的肺腺癌且有可测量病变（根据RECIST 1.1标准≥10毫米）。在静脉注射327 MBq（范围299 - 399 MBq）的F - AzaFol后3、11、18、30、40、50和60分钟采集TOF - PET图像以确定剂量。使用OLINDA/EXM v.2.0软件评估器官吸收剂量（AD）、肿瘤AD和患者有效剂量（E），并与临床前结果进行比较。
未观察到严重的相关不良事件。最高的AD出现在肝脏、肾脏、膀胱和脾脏（分别为51.9、45.8、39.1和35.4 μGy/MBq）。估计的患者和性别平均E分别为18.0±2.6和19.7±1.4 μSv/MBq。人体中的E超过了从临床前数据推断的14.0 μSv/MBq的值。平均肿瘤AD为34.8 μGy/MBq（范围13.6 - 60.5 μGy/MBq）。
F - Azafol是一种PET剂，具有良好的剂量学特性，对患者的辐射剂量负担合理，值得进一步评估以评估其性能。
ClinicalTrial.gov，NCT03242993，于2017年8月8日发布。
