Purpose

A novel cystine-knot peptide–based PET radiopharmaceutical, ¹⁸F-FP-R₀1-MG-F2 (knottin), was developed to selectively bind to human integrin α_vβ₆ which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of ¹⁸F-FP-R₀1-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_max) and mean SUV (SUV_mean) 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 ¹⁸F-FP-R₀1-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUV_mean: 9.7–14.5). Intermediate uptake was found in the normal pancreas (average SUV_mean: 4.5). Mild uptake was found in the lungs and liver (average SUV_mean < 1.0). The effective dose was calculated to be 2.538 × 10⁻² 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

¹⁸F-FP-R₀1-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 ¹⁸F-FP-R₀1-MG-F2 PET is feasible, but larger studies are required to define the role of this approach.

Trial registration

NCT02683824.

中文翻译：

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使用基于胱氨酸结肽的 18F-FP-R01-MG-F2 靶向胰腺癌患者整合素 αvβ6 的试验阶段 PET/CT 研究

目的

开发了一种基于胱氨酸结肽的新型 PET 放射性药物¹⁸ F-FP-R ₀ 1-MG-F2（knottin），以选择性结合在胰腺癌中过表达的人整合素 α _v β _{6 。}本研究的目的是评估¹⁸ F-FP-R ₀ 1-MG-F2 在胰腺癌患者中的安全性、生物分布、剂量测定和病变吸收。

方法

在 2017 年 3 月至 2021 年 2 月期间，前瞻性纳入了 15 名经组织学证实的胰腺癌患者（6 名男性，9 名女性）并接受了 knottin PET/CT（ClinicalTrials.gov 标识符 NCT02683824）。在成像扫描前后收集生命体征和实验室结果。在每位患者的 24 个正常组织和胰腺癌病灶中测量了最大标准化摄取值 (SUV _max ) 和平均 SUV (SUV _{mean )。}根据生物分布数据，使用 OLINDA/EXM 软件计算器官剂量和全身有效剂量。

结果

生命体征或实验室值没有显着变化可定义为不良事件或严重不良事件。注射后 1 小时，¹⁸ F-FP-R ₀ 1-MG-F2 高摄取区域包括垂体、胃、十二指肠、肾脏和膀胱（平均 SUV_平均值：9.7–14.5）。在正常胰腺中发现中间摄取（平均 SUV_平均值：4.5）。在肺和肝脏中发现轻度吸收（平均 SUV_平均值 < 1.0）。有效剂量计算为 2.538 × 10 ^-2 毫希沃特/MBq。Knottin PET/CT 在 15 名患者中检测到所有已知的胰腺肿瘤，尽管它没有检测到手术中有淋巴结转移的三名患者中有两名的短径小于 1 厘米的小胰周淋巴结。Knottin PET/CT 检测到肺部 ( n  = 5)、肝脏 ( n  = 4) 和腹膜 ( n  = 2) 的远处转移，并通过活检和/或对比增强 CT 证实。

结论

¹⁸ F-FP-R ₀ 1-MG-F2 是一种安全的 PET 放射性药物，其有效剂量可与其他诊断剂相媲美。^用18 F-FP-R ₀ 1-MG-F2 PET评估原发性胰腺癌和远处转移是可行的，但需要更大规模的研究来确定这种方法的作用。

试用注册

NCT02683824。