Chemical Exchange Saturation Transfer Contrast Agents for Magnetic Resonance Imaging

Sherry, A. Dean; Woods, Mark

doi:10.1146/annurev.bioeng.9.060906.151929

Cited by 322 publications

(339 citation statements)

References 80 publications

(77 reference statements)

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“…At present the main clinically used agents from this list are PET and SPECT radioligands; however, there are a number of MRI (hyperpolarized, CEST, and PARACEST) agents and optical agents showing promise in preclinical and clinical studies. Please refer to the following literature for examples of small molecule imaging agents for PET (142,143,166,350), SPECT (164,232), MRI (5,148,227,381), and optical (61,382) imaging studies.…”

Section: B Small Moleculesmentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

940

954

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Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.

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Section: B Small Moleculesmentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

940

954

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“…However, newly designed PARACEST agents promise to increase detection sensitivity (40), and in combination with the ability to modulate contrast by selective excitation, PARACEST agents may have many biologic and medical applications.…”

Section: Resultsmentioning

confidence: 99%

Optimized MRI contrast for on‐resonance proton exchange processes of PARACEST agents in biological systems

Suchý

Jones

et al. 2009

Magnetic Resonance in Med

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Image contrast associated with paramagnetic chemical exchange saturation transfer agents can be generated by off-resonance irradiation of agent-bound water or amide protons or on-resonance irradiation of bulk water. Previously, a four-pool model was developed to describe an in vivo system. The model incorporated the magnetization transfer effect from macromolecules when using off-resonance irradiation. In the current study, this four-pool model is modified to describe the in vivo system when using on-resonance irradiation. The influences of pulse power, pulse duration, the chemical shift of bound water, the proton exchange rate between bulk water and bound water, and agent concentration on the on-resonance paramagnetic agent chemical exchange effects were simulated using a WALTZ-16 pulse train in the absence and presence of the macromolecule pool. The results demonstrated that while contrast increases with pulse duration in aqueous solution, there is an optimal pulse duration that maximizes on-resonance paramagnetic agent chemical exchange effects contrast in vivo. Diamagnetic and paramagnetic chemical exchange saturation transfer (PARACEST) (1-12) agents have many possible medical and biologic applications, including the measurement of tissue pH based on the pH dependence of the exchange rate of amide protons with bulk water protons (13-15), the measurement of tissue temperature using the linear dependence of the bound water chemical shift on temperature (16,17), enzymatic activity (18), and metabolite levels (19-21). The CEST detection sensitivity (or CEST effect) is defined as the change in the bulk water signal intensity of the agent solution following irradiation of the exchangeable protons. The PARACEST effect and the chemical shift of bound protons can be modified using different metals in the lanthanide series or ligands (22). Currently, the most efficient PARACEST agents are europium (Eu 3ϩ ) based, with a bound water chemical shift around 45 parts per million (ppm) and visible CEST contrast from millimolar concentrations.Despite the large chemical shift of the bound water and amide protons associated with PARACEST agents, the relatively high saturation power needed for in vivo PARAC-EST imaging results in the simultaneous observation of inherent magnetization transfer (MT) from macromolecule-bound protons (17,23). Though dysprosium-, thulium (Tm 3ϩ )-, and ytterbium-based PARACEST agents have bound water chemical shifts beyond the MT effect range, the fast proton exchange between the bound water of these compounds and the bulk water results in an undetectable CEST signal within specific absorption rate power limits. However, the irradiation of bulk water (on-resonance) in solutions with fast proton exchange between bound water and bulk water may also produce contrast due to chemical exchange (24).The detected effect of a PARACEST agent based on the radiofrequency (RF) excitation of bulk water was previously described as the on-resonance paramagnetic agent chemical exchange effect (OPARACHEE) to differe...

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“…39 Chemical exchange saturation transfer is a new method of generating MR contrast that relies on the chemical exchange of protons of solutes with bulk water, which reduces MR imaging signal intensity. 40 Gilad and associates 41ˆr st described a lysine-rich protein (LRP) gene, a CEST-based reporter gene, detecting LRP-expressing xenografts in mouse brain. The CEST-based reporter gene is of particular interest because it is can be switched and would allow``multicolor'' imaging.…”

Section: Mr Imaging Reporter Genesmentioning

confidence: 99%

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

2010

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Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic e‹cacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene.

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Chemical Exchange Saturation Transfer Contrast Agents for Magnetic Resonance Imaging

Cited by 322 publications

References 80 publications

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Optimized MRI contrast for on‐resonance proton exchange processes of PARACEST agents in biological systems

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

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