Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial].

IF 8.6 1区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2025-01-01 Epub Date: 2024-10-11 DOI:10.1007/s00259-024-06947-9

I Schmidt, R A Vergeer, M R Postma, G van den Berg, A J Sterkenburg, A G W Korsten-Meijer, R A Feijen, S Kruijff, A P van Beek, W F A den Dunnen, D J Robinson, J M C van Dijk, W B Nagengast, J M A Kuijlen

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引用次数: 0

Abstract

Purpose: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A).

Methods: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed.

Results: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression.

Conclusion: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group.

Trial registration: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

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使用贝伐单抗-800CW在内窥镜经蝶窦手术中荧光检测垂体神经内分泌肿瘤：一项非随机、非盲法、单中心可行性和剂量发现试验[DEPARTURE试验]。

目的：对于有海绵窦侵犯的垂体神经内分泌肿瘤（PitNET），通过全切实现内分泌缓解具有挑战性。本研究旨在评估术中荧光成像的安全性、可行性和最佳剂量，作为使用贝伐珠单抗-800CW（靶向血管内皮生长因子A（VEGF-A））从周围组织中区分PitNET的附加工具：方法：在第一部分中，对 4 组 3 名 Knosp 3-4 级 PitNET 患者进行了剂量递增（0-4∙5-10-25 毫克）。在第二部分中，经过中期分析后，10 毫克和 25 毫克组扩大到总共 6 名患者。定量荧光分子内镜检查包括宽视野荧光分子内镜检查和多直径单纤维反射/单纤维荧光光谱检查。计算新鲜手术标本的平均荧光强度（MFI），并进行血管内皮生长因子染色：结果：共纳入 18 名患者。所有剂量的耐受性均良好。共发生了三起严重不良事件，但均与示踪剂无关。第一部分显示，10 毫克（TBR 2∙00 [1∙86, 2∙19]）和 25 毫克（TBR 2∙10, [1∙86, 2∙58]）的体内肿瘤-背景比值均足够高。第二部分显示，25 毫克组的 MFI 要高得多。在 10 毫克和 25 毫克组中，肿瘤与周围组织之间的差异均有统计学意义（p 结论：该研究证明了肿瘤治疗的安全性和可行性：这项研究证明了在 PitNET 手术中进行定量荧光分子内窥镜检查的安全性和可行性。10毫克和25毫克贝伐珠单抗-800CW均可在体内明确分化，25毫克组的体内外对比度（MFI）有所提高：NCT04212793 / 研究详情| 在TSS期间使用贝伐单抗800CW检测PitNET组织| ClinicalTrials.gov.

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来源期刊

European Journal of Nuclear Medicine and Molecular Imaging 医学-核医学

CiteScore

15.60

自引率

9.90%

发文量

392

审稿时长

3 months

期刊介绍： The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.