一种靶向抗αβ整合素近红外荧光染料用于犬自然发生的软组织肉瘤荧光引导切除的评估。

Evaluation of a targeted anti-αβ integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs.

作者信息

Beer Patricia, Grest Paula, Krudewig Christiane, Staudinger Chris, Ohlerth Stefanie, Rohrer Bley Carla, Jarosch Armin, Ech-Cherif Houria, Markkanen Enni, Park Brian, Nolff Mirja Christine

机构信息

Clinic for Small Animal Surgery, Vetsuisse Faculty, University Animal Hospital, University of Zurich, Zurich, Switzerland.

Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

出版信息

Eur J Nucl Med Mol Imaging. 2025 Feb;52(3):1137-1148. doi: 10.1007/s00259-024-06953-x. Epub 2024 Oct 22.

DOI:10.1007/s00259-024-06953-x

PMID:39436437

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11754361/

Abstract

PURPOSE

Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-αβ integrin targeting near-infrared fluorescent (NIRF) dye (Angiostamp800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity.

METHODS

Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3 cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios.

RESULTS

A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratio of 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001).

CONCLUSION

Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

摘要

目的

完整切除是软组织肉瘤（STS）患者生存的关键预后因素，在人类和伴侣动物中均如此。荧光引导手术可提高切除准确性。由于犬类经常受到STS影响，它们可作为模型来测试一种靶向抗αβ整合素的近红外荧光（NIRF）染料（Angiostamp800）用于STS的荧光引导手术，以评估其在犬类中的安全性和可行性，以及与标准治疗相比，在手术完整性和局部复发方面是否能转化为临床相关益处。此外，我们旨在关联靶点表达与NIRF信号强度。

方法

20只患有STS的犬术前随机分为两组，分别接受Angiostamp™（NIRF组）或生理盐水（对照组）。研究人员对治疗分组不知情，必要时根据NIRF信号调整切除范围。在距肿瘤边缘1 cm和3 cm处进行组织学检查以确定切缘状态。在原发组织活检和福尔马林固定组织中测量肿瘤与背景的比率。将荧光区域与经组织学证实的相应肿瘤区域进行比较，使用Dice系数进行分析。通过免疫组织化学对靶点表达进行定量，并与NIRF信号比率相关联。

结果

NIRF组的所有10个肿瘤均检测到荧光信号，原发活检中肿瘤与背景的比率为7.4±5.8，福尔马林固定组织中为13.5±10.9。在NIRF组中，10例中有5例根据荧光信号调整了切除范围，其中4例实现了完整切除并避免了R1切除。NIRF组和对照组的10例切除中有9例和8例为R0切除，每组各有1例局部复发，NIRF组有1例与肉瘤相关的死亡。NIRF信号与经组织学证实的肿瘤区域相关（Dice系数为0.75±0.17）。肿瘤组织中的靶点表达高于瘤周组织（p<0.0003），且与NIRF信号呈中度相关（r = 0.6516，p<0.0001）。