Advanced molecular imaging for the characterisation of complex medicines

Yilmaz, Duygu; Sharp, Paul; Main, Martin J.; Simpson, Peter B.

doi:10.1016/j.drudis.2022.03.001

Cited by 3 publications

(2 citation statements)

References 65 publications

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“…Nowadays, various imaging technologies, such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), are used for the evaluations of diagnosis and therapy [ 1 , 2 ]. Among them, MRI, a routinely used imaging modality effective for both anatomical and functional imaging of diseased soft tissues, including solid tumors, offers many advantages owing to its high spatial and temporal resolution [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Preparation and In Vitro Evaluation of a Gadolinium-Containing Vitamin E TPGS Micelle as a Potential Contrast Agent for MR Imaging

Gai

et al. 2023

Pharmaceutics

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The application of many currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) has been limited because of their bio-incompatibility and toxicity. The aim of this study is to synthesize and characterize a new micelle-based TPGS gadolinium chelate as a biocompatible MRI contrast agent for prolonged blood circulation time and good tumor imaging contrast. The TPGS-gadolinium conjugate was prepared through the conjugation between TPGS-SA and bifunctional L-NETA-Gd chelate. The conjugate was characterized with regard to molecular weight, critical micellar concentration and particle sizes, cellular uptake, and in vitro cell MRI. Distributions of the MRI contrast agent in various organs were determined via intravenous injection of the agent into mice bearing xenograft tumors. The successfully prepared TPGS-L-NETA-Gd micelle exhibited improved cellular uptake in HepG2 cells and xenografts and high in vivo safety. Distributions of TPGS-L-NETA-Gd in mice showed enhanced cellular uptake up to 2 h after the contrast agent injection. Its in vitro and in vivo properties make it a favorable macromolecular MRI contrast agent for future in vivo imaging.

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Section: Introductionmentioning

confidence: 99%

Preparation and In Vitro Evaluation of a Gadolinium-Containing Vitamin E TPGS Micelle as a Potential Contrast Agent for MR Imaging

Gai

et al. 2023

Pharmaceutics

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“…Expanding and validating models for use in transport studies is non-trivial, as highlighted by recent accounts showing that it is paramount to perform a comprehensive validation as they often are limited by poor abilities to predict the in vivo level of drug transport (Dahlgren et al, 2015). Together this highlights how there are still room for new methodologies facilitating the study of in vitro drug transport in validated, easy-to-use and reproducible platforms (Gleeson and McCartney, 2019), especially compatible with real-time fluorescent imaging (Wong et al, 2020;Halamoda-Kenzaoui et al, 2021;Larsen et al, 2021;Yilmaz et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Quantifying the transport of biologics across intestinal barrier models in real-time by fluorescent imaging

Weller

Hansen

Marie

et al. 2022

Front. Bioeng. Biotechnol.

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Unsuccessful clinical translation of orally delivered biological drugs remains a challenge in pharmaceutical development and has been linked to insufficient mechanistic understanding of intestinal drug transport. Live cell imaging could provide such mechanistic insights by directly tracking drug transport across intestinal barriers at subcellular resolution, however traditional intestinal in vitro models are not compatible with the necessary live cell imaging modalities. Here, we employed a novel microfluidic platform to develop an in vitro intestinal epithelial barrier compatible with advanced widefield- and confocal microscopy. We established a quantitative, multiplexed and high-temporal resolution imaging assay for investigating the cellular uptake and cross-barrier transport of biologics while simultaneously monitoring barrier integrity. As a proof-of-principle, we use the generic model to monitor the transport of co-administrated cell penetrating peptide (TAT) and insulin. We show that while TAT displayed a concentration dependent difference in its transport mechanism and efficiency, insulin displayed cellular internalization, but was restricted from transport across the barrier. This illustrates how such a sophisticated imaging based barrier model can facilitate mechanistic studies of drug transport across intestinal barriers and aid in vivo and clinical translation in drug development.

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Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation

Dhoundiyal,

Srivastava,

Kumar

et al. 2024

Eur J Med Res

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This review article explores the dynamic field of radiopharmaceuticals, where innovative developments arise from combining radioisotopes and pharmaceuticals, opening up exciting therapeutic possibilities. The in-depth exploration covers targeted drug delivery, delving into passive targeting through enhanced permeability and retention, as well as active targeting using ligand-receptor strategies. The article also discusses stimulus-responsive release systems, which orchestrate controlled release, enhancing precision and therapeutic effectiveness. A significant focus is placed on the crucial role of radiopharmaceuticals in medical imaging and theranostics, highlighting their contribution to diagnostic accuracy and image-guided curative interventions. The review emphasizes safety considerations and strategies for mitigating side effects, providing valuable insights into addressing challenges and achieving precise drug delivery. Looking ahead, the article discusses nanoparticle formulations as cutting-edge innovations in next-generation radiopharmaceuticals, showcasing their potential applications. Real-world examples are presented through case studies, including the use of radiolabelled antibodies for solid tumors, peptide receptor radionuclide therapy for neuroendocrine tumors, and the intricate management of bone metastases. The concluding perspective envisions the future trajectory of radiopharmaceuticals, anticipating a harmonious integration of precision medicine and artificial intelligence. This vision foresees an era where therapeutic precision aligns seamlessly with scientific advancements, ushering in a new epoch marked by the fusion of therapeutic resonance and visionary progress. Graphical Abstract

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Advanced molecular imaging for the characterisation of complex medicines

Cited by 3 publications

References 65 publications

Preparation and In Vitro Evaluation of a Gadolinium-Containing Vitamin E TPGS Micelle as a Potential Contrast Agent for MR Imaging

Preparation and In Vitro Evaluation of a Gadolinium-Containing Vitamin E TPGS Micelle as a Potential Contrast Agent for MR Imaging

Quantifying the transport of biologics across intestinal barrier models in real-time by fluorescent imaging

Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation

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