基于胱氨酸结肽的 F-FP-R1-MG-F2 靶向整合素 αβ 的胰腺癌患者的初步 PET/CT 研究。
Pilot-phase PET/CT study targeting integrin αβ in pancreatic cancer patients using the cystine-knot peptide-based F-FP-R1-MG-F2.
机构信息
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA, 94305-5281, USA.
Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305-5281, USA.
出版信息
Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):184-193. doi: 10.1007/s00259-021-05595-7. Epub 2021 Nov 3.
PURPOSE
A novel cystine-knot peptide-based PET radiopharmaceutical, F-FP-R1-MG-F2 (knottin), was developed to selectively bind to human integrin αβ which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of F-FP-R1-MG-F2 in patients with pancreatic cancer.
METHODS
Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUV) and mean SUV (SUV) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software.
RESULTS
There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high F-FP-R1-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUV: 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUV: 4.5). Mild uptake was found in the lungs and liver (average SUV < 1.0). The effective dose was calculated to be 2.538 × 10 mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n = 5), liver (n = 4), and peritoneum (n = 2), confirmed by biopsy and/or contrast-enhanced CT.
CONCLUSION
F-FP-R1-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with F-FP-R1-MG-F2 PET is feasible, but larger studies are required to define the role of this approach.
TRIAL REGISTRATION
NCT02683824.
目的
开发了一种新型的半胱氨酸环肽基 PET 放射性药物 F-FP-R1-MG-F2（knottin），用于选择性结合在胰腺癌中过度表达的人整合素 αβ。本研究旨在评估 F-FP-R1-MG-F2 在胰腺癌患者中的安全性、生物分布、剂量学和病灶摄取。
方法
15 名经组织学证实的胰腺癌患者（6 名男性，9 名女性）于 2017 年 3 月至 2021 年 2 月前瞻性入组并接受 knottin PET/CT（ClinicalTrials.gov 标识符 NCT02683824）。在成像扫描前后采集生命体征和实验室结果。为每位患者的 24 个正常组织和胰腺癌病灶测量最大标准化摄取值（SUV）和平均 SUV（SUV）。从生物分布数据中，使用 OLINDA/EXM 软件计算器官剂量和全身有效剂量。
结果
无符合不良事件或严重不良事件标准的生命体征或实验室值的显著变化。在注射后 1 小时，高 F-FP-R1-MG-F2 摄取区域包括垂体、胃、十二指肠、肾脏和膀胱（平均 SUV：9.7-14.5）。正常胰腺的摄取为中等（平均 SUV：4.5）。肺和肝脏的摄取为轻度（平均 SUV<1.0）。有效剂量计算为 2.538×10-3mSv/MBq。knottin PET/CT 在 15 名患者中均检测到所有已知的胰腺肿瘤，但在 3 名有淋巴结转移的患者中，有 2 名患者的手术中小于 1cm 短径的胰周小淋巴结未检测到。knottin PET/CT 检测到肺（n=5）、肝（n=4）和腹膜（n=2）远处转移，通过活检和/或增强 CT 证实。
结论
F-FP-R1-MG-F2 是一种安全的 PET 放射性药物，其有效剂量与其他诊断剂相当。使用 F-FP-R1-MG-F2 PET 评估原发性胰腺癌和远处转移是可行的，但需要更大的研究来确定这种方法的作用。
试验注册
NCT02683824。
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