PanLN800(-Forte)是一种用于术中泛淋巴结成像的阳离子七甲基吲哚菁荧光造影剂。

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Robin A Faber, Victor M Baart, Mark W Bordo, Taryn L March, Adrianus R P M Valentijn, Stefan Harmsen, Martin Pool, Jacobus Burggraaf, John V Frangioni, Alexander L Vahrmeijer
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引用次数: 0

摘要

恶性肿瘤的准确分期往往需要对淋巴结进行全面的评估。然而,在肿瘤手术中发现这些淋巴结是一项艰巨而耗时的任务,这增加了遗漏淋巴结和并发症的风险。使用实验荧光造影剂PanLN800(-Forte)进行近红外(NIR)荧光成像可以实时识别淋巴结,并可能解决这一长期存在的问题。在本研究中,我们对PanLN800(-Forte)进行了临床前毒理学评估,以确定其在胸外科术中泛淋巴结成像中的临床应用。方法:采用单次延长剂量毒理学研究,确定单次静脉给药PanLN800(-Forte)对Wistar Han大鼠的安全性和潜在毒性。研究分为对照组和两个治疗组(5.0 mg/kg和15.0 mg/kg PanLN800(-Forte)),每组10只雄性和10只雌性。实验终点包括死亡率/死亡率、临床体征、体重、体重增加、临床病理、毒性和大体尸检观察。结果:大鼠给药5.0 mg/kg PanLN800(-Forte)后出现意外急性死亡。经大体尸检和病理观察,未发现明确的猝死原因。为了了解PanLN800(-Forte)的毒性机制,进行了几项附加试验。通过消除,急性心脏毒性似乎是大鼠急性死亡的原因,其中PanLN800(-Forte)被发现是一种有效的肌力,可作为心脏钙增敏剂。结论:由于心脏钙致敏,PanLN800(-Forte)不是一种可行的手术淋巴结成像荧光造影剂,但可能是一种治疗心力衰竭的新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiac inotropy and cardiac calcium sensitization of PanLN800(-Forte), a cationic heptamethine indocyanine fluorescent contrast agent for intraoperative pan lymph node imaging.

Introduction: Accurate staging of malignancies often requires comprehensive evaluation of lymph nodes. However, finding these lymph nodes during oncological surgery is a daunting and time-consuming task, which increases the risk of missed lymph nodes and complications. Near-infrared (NIR) fluorescence imaging with the experimental fluorescent contrast agent PanLN800(-Forte) could provide real-time identification of lymph nodes and may solve this longstanding problem. In the current study we performed the preclinical toxicology evaluation of PanLN800(-Forte) towards its clinical translation for intraoperative pan lymph node imaging in thoracic surgery.

Methods: A single extended dose toxicology study was conducted to determine the safety and potential toxicity of PanLN800(-Forte) after administration of a single intravenous dose to Wistar Han rats. The study included a control group and two treatment groups (5.0 mg/kg and 15.0 mg/kg PanLN800(-Forte)), each consisting of 10 male and 10 female rats. Experimental endpoints included moribundity/mortality, clinical signs, body weights, body weight gains, clinical pathology, toxicity, and gross necropsy observations.

Results: Unexpected acute mortality was observed after administration of 5.0 mg/kg PanLN800(-Forte) to rats. No clear cause of sudden death was found after gross necropsy and pathology observations. To understand the mechanism of toxicity of PanLN800(-Forte), several additional tests were performed. By elimination, acute cardiac toxicity appears to be the cause of acute mortality in rats, in which PanLN800(-Forte) was found to be a potent inotrope acting as a cardiac calcium sensitizer.

Conclusion: PanLN800(-Forte) is not a viable fluorescent contrast agent for lymph node imaging in surgery because of cardiac calcium sensitization but may be a novel treatment for heart failure.

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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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