一种新型双模态造影剂在啮齿动物模型中的临床前研究。

A preclinical study of a novel dual-modality contrast agent in rodent models.

作者信息

Zhou Xuelai, Jiang Kangli, Han Yuxin, Yang Shuxu

机构信息

Zhejiang Poly Pharm. Co., Ltd., Hangzhou, China.

Department of Neurosurgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Front Bioeng Biotechnol. 2025 Mar 20;13:1557772. doi: 10.3389/fbioe.2025.1557772. eCollection 2025.

Abstract

INTRODUCTION

Glioblastoma (GBM) represents the most aggressive and prevalent form of primary malignant brain tumor in adults, with surgical intervention being the primary treatment modality. To enhance surgical outcomes and extend patient survival, we have engineered a dual-modality MRI/FI contrast agent known as PL002 to aid in the surgical management of GBM.

METHODS

In this study, an orthotopic glioma model was established in mice via intracranial injection of U-87 MG cells. Subsequently, the model animals were intravenously injected with PL002 and placed in a 7.0T magnetic resonance imaging (MRI) device to evaluate the imaging effects. After the MRI scan, fluorescence imaging techniques were employed to observe the distribution of PL002 at both the brain tissue and cellular levels. Moreover, healthy rat models were utilized to investigate the pharmacokinetic characteristics, tissue distribution, and safety profile of PL002.

RESULTS

The molecular structure of PL002 contains both gadolinium (Gd) and indocyanine green (ICG), demonstrating optimal imaging effects within the dosage range of 10-50 mg/kg, with a half-life of 2.51 to 4.87 hours. Even at relatively low concentrations in the brain, PL002 can provide stable and sustained support for MRI and fluorescence imaging for up to 72 hours. No abnormalities were observed in rats at a dosage of 100 mg/kg.

DISCUSSION

Compared to Gadavist® and ICG, PL002 provided sustained support for MRI and FI of GBM for 72 h, with a broad therapeutic window. This dual-modality contrast agent holds significant potential and promise for applications in preoperative assessment of resection margins, real-time intraoperative guidance, and postoperative verification of the extent of resection.

摘要

引言

胶质母细胞瘤(GBM)是成人原发性恶性脑肿瘤中最具侵袭性和最常见的形式,手术干预是主要的治疗方式。为了提高手术效果并延长患者生存期,我们设计了一种名为PL002的双模态MRI/FI造影剂,以辅助GBM的手术治疗。

方法

在本研究中,通过颅内注射U-87 MG细胞在小鼠中建立原位胶质瘤模型。随后,给模型动物静脉注射PL002,并将其置于7.0T磁共振成像(MRI)设备中以评估成像效果。MRI扫描后,采用荧光成像技术观察PL002在脑组织和细胞水平的分布。此外,利用健康大鼠模型研究PL002的药代动力学特征、组织分布和安全性。

结果

PL002的分子结构同时包含钆(Gd)和吲哚菁绿(ICG),在10-50 mg/kg的剂量范围内显示出最佳成像效果,半衰期为2.51至4.87小时。即使在脑中浓度相对较低时,PL002也能为MRI和荧光成像提供长达72小时的稳定持续支持。在100 mg/kg的剂量下,大鼠未观察到异常。

讨论

与Gadavist®和ICG相比,PL002为GBM的MRI和FI提供了72小时的持续支持,具有较宽的治疗窗口。这种双模态造影剂在切除边缘的术前评估、实时术中引导以及切除范围的术后验证应用中具有巨大潜力和前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f63d/11966174/dc8fd7c83ab0/fbioe-13-1557772-g001.jpg

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