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

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1557772

Xuelai Zhou, Kangli Jiang, Yuxin Han, Shuxu Yang

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引用次数: 0

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 (Gd³⁺) 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.

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.