Activatable <sup>19</sup>F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects

Lin, Hongyu; Tang, Xiaoxue; Li, Ao; Gao, Jinhao

doi:10.1002/adma.202005657

Cited by 48 publications

(49 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This Account summarizes efforts in our lab over the past decade to develop nextgeneration FC NE cell detection probes. Next-generation FCbased cell detection probes will have improved sensitivity and specificity and be activatable 45 and vector-capable, 46 while retaining a focus on scalability and near-term translatability 47 . Resulting probes will be effective for interrogating aspects of the initial biodistribution of cell therapy and inflammation detection.…”

Section: Discussionmentioning

confidence: 99%

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

2021

View full text Add to dashboard Cite

Metrics & More Article RecommendationsCONSPECTUS: This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as chelators, fluorophores, and peptides, that are soluble in FC oils. These materials have helped transform the field of in vivo molecular imaging by enabling sensitive and cell-specific imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescence detection. FC emulsions, historically considered for artificial blood substitutes, are routinely used for ultrasound imaging in clinic and have a proven safety profile and a well-characterized biodistribution and pharmacokinetics. The inertness of fluorocarbons contributes to their low toxicity but makes functionalization difficult. The high electronegativity of fluorine imparts very low cohesive energy density and Lewis basicity to heavily fluorinated compounds, making dissolution of metal ions and organic molecules challenging. Functionalization is further complicated by colloidal instability toward heat and pH, as well as limited availability of biocompatible surfactants.We have devised new fluorous chelators that overcome solubility barriers and are able to bind a range of metal ions with high thermodynamic stability and biocompatibility. NE harboring chelators in the fluorous phase are a powerful platform for the development of multimodal imaging agents. These compositions rapidly capture metal ions added to the aqueous phase, thereby functionalizing NEs in useful ways. For example, Fe 3+ encapsulation imparts a strong paramagnetic relaxation effect on 19 F T 1 that dramatically accelerates 19 F MRI data acquisition times and hence sensitivity in cell tracking applications. Alternatively, 89 Zr encapsulation creates a sensitive and versatile PET probe for inflammatory macrophage detection. Adding lanthanides, such as Eu 3+ , renders NE luminescent. Beyond chelators, this Account further covers our progress in formulating NEs with fluorophores, such as cyanine or BODIPY dyes, with their utility demonstrated in fluorescence imaging, biosensing, flow cytometry and histology. Fluorous dyes soluble in FC oils are also key enablers for nascent whole-body imaging technologies such as cryo-fluorescence tomography (CFT). Additionally, fluorous cell-penetrating peptides inserted on the NE surface increase the uptake of NE by ∼8fold in weakly phagocytic stem cells and lymphocytes used in immunotherapy, resulting in significant leaps in detection sensitivity in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

2021

View full text Add to dashboard Cite

show abstract

“…Similar to Traditional proton ( 1 H) MRI, 19 F MRI produces imaging signals by detecting the magnetic field changes which are accompanied by that 19 F atoms return from the excited state to the ground state after the withdrawal of the radio frequency pulse [174]. 1 H MRI is able to present abundant anatomical and pathophysiological information, but it shows limited capabilities to visualize key cells and biomolecules which tend to be rare [175].…”

Section: F Mrimentioning

confidence: 99%

Recent development of contrast agents for magnetic resonance and multimodal imaging of glioblastoma

Zhuang

Zhang

2022

J Nanobiotechnol

View full text Add to dashboard Cite

Glioblastoma (GBM) as the most common primary malignant brain tumor exhibits a high incidence and degree of malignancy as well as poor prognosis. Due to the existence of formidable blood–brain barrier (BBB) and the aggressive growth and infiltrating nature of GBM, timely diagnosis and treatment of GBM is still very challenging. Among different imaging modalities, magnetic resonance imaging (MRI) with merits including high soft tissue resolution, non-invasiveness and non-limited penetration depth has become the preferred tool for GBM diagnosis. Furthermore, multimodal imaging with combination of MRI and other imaging modalities would not only synergistically integrate the pros, but also overcome the certain limitation in each imaging modality, offering more accurate morphological and pathophysiological information of brain tumors. Since contrast agents contribute to amplify imaging signal output for unambiguous pin-pointing of tumors, tremendous efforts have been devoted to advances of contrast agents for MRI and multimodal imaging. Herein, we put special focus on summary of the most recent advances of not only MRI contrast agents including iron oxide-, manganese (Mn)-, gadolinium (Gd)-, 19F- and copper (Cu)-incorporated nanoplatforms for GBM imaging, but also dual-modal or triple-modal nanoprobes. Furthermore, potential obstacles and perspectives for future research and clinical translation of these contrast agents are discussed. We hope this review provides insights for scientists and students with interest in this area. Graphical abstract

show abstract

“…19 F MRI is of particular interest, because there is negligible endogenous 19 F background ( 214 ), the accumulation of 19 F-atoms results in a true positive contrast that can be quantified and does not impair anatomical, functional and parametric 1 H MRI. Additionally, 19 F MRI is very versatile and multiple interesting approaches just recently emerged in the preclinical field like multispectral 19 F MRI, environmental responsive smart probes or active targeting of 19 F tracers ( 215 , 216 ).…”

Section: From Bench To Bedsidementioning

confidence: 99%

A Toolbox to Investigate the Impact of Impaired Oxygen Delivery in Experimental Disease Models

et al. 2022

View full text Add to dashboard Cite

Impaired oxygen utilization is the underlying pathophysiological process in different shock states. Clinically most important are septic and hemorrhagic shock, which comprise more than 75% of all clinical cases of shock. Both forms lead to severe dysfunction of the microcirculation and the mitochondria that can cause or further aggravate tissue damage and inflammation. However, the detailed mechanisms of acute and long-term effects of impaired oxygen utilization are still elusive. Importantly, a defective oxygen exploitation can impact multiple organs simultaneously and organ damage can be aggravated due to intense organ cross-talk or the presence of a systemic inflammatory response. Complexity is further increased through a large heterogeneity in the human population, differences in genetics, age and gender, comorbidities or disease history. To gain a deeper understanding of the principles, mechanisms, interconnections and consequences of impaired oxygen delivery and utilization, interdisciplinary preclinical as well as clinical research is required. In this review, we provide a “tool-box” that covers widely used animal disease models for septic and hemorrhagic shock and methods to determine the structure and function of the microcirculation as well as mitochondrial function. Furthermore, we suggest magnetic resonance imaging as a multimodal imaging platform to noninvasively assess the consequences of impaired oxygen delivery on organ function, cell metabolism, alterations in tissue textures or inflammation. Combining structural and functional analyses of oxygen delivery and utilization in animal models with additional data obtained by multiparametric MRI-based techniques can help to unravel mechanisms underlying immediate effects as well as long-term consequences of impaired oxygen delivery on multiple organs and may narrow the gap between experimental preclinical research and the human patient.

show abstract

Activatable ¹⁹F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects

Cited by 48 publications

References 64 publications

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Recent development of contrast agents for magnetic resonance and multimodal imaging of glioblastoma

A Toolbox to Investigate the Impact of Impaired Oxygen Delivery in Experimental Disease Models

Contact Info

Product

Resources

About

Activatable 19F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects

Cited by 48 publications

References 64 publications

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Recent development of contrast agents for magnetic resonance and multimodal imaging of glioblastoma

A Toolbox to Investigate the Impact of Impaired Oxygen Delivery in Experimental Disease Models

Contact Info

Product

Resources

About

Activatable ¹⁹F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects