Artificial reporter gene providing MRI contrast based on proton exchange

Gilad, Assaf A.; McMahon, Michael T.; Walczak, Piotr; Winnard, Paul T.; Raman, Venu; Laarhoven, Hanneke W. M. van; Skoglund, Cynthia M; Bulte, Jeff W.M.; Zijl, Peter C.M. van

doi:10.1038/nbt1277

Cited by 384 publications

(441 citation statements)

References 15 publications

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“…Proof of concept was recently reported. 47 However, all these novel developments, although very promising in terms of contrast improvement, raise a lot of questions about toxic and immunologic side effects. For these reasons, the standard, safe CAs studied here and clinically approved for i.v.…”

Section: Discussionmentioning

confidence: 99%

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

et al. 2009

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“…After injection into mice carrying s.c. xenograft tumors, these strains, in conjunction with bioluminescent 3D optical tomography combined with micro-CT scanning, were used to visualize the malignant growths. To reach deeper tissues in patients and even multiplex output, next-generation systems could be extended to the expression of protein-based contrast agents (45,(54)(55)(56). Using heme-binding proteins and other reporters from functional magnetic resonance imaging, future applications could possibly report from deeper tissue, using orthologous reporters for greater information retrieval.…”

Section: In Vivo Diagnosticsmentioning

confidence: 99%

Synthetic biology devices for in vitro and in vivo diagnostics

Slomovic

Pardee

Collins

2015

Proc. Natl. Acad. Sci. U.S.A.

301

228

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There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.synthetic biology | diagnostics | biosensing | synthetic gene networks | nanobiotechnology

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“…k 1c ϭ 1/T 1c ϩ k ca [18] k 1d ϭ 1/T 1d ϩ k da [19] k 2a ϭ 1/T 2a ϩ k ab ϩ k ac ϩ k ad [20] k 2b ϭ 1/T 2b ϩ k ba [21] k 2c ϭ 1/T 2c ϩ k ca [22] k 2d ϭ 1/T 2d ϩ k da [23] T 1i and T 2i are the longitudinal and transverse relaxation times of pool i, i is the lifetime of protons in pool i, a is the frequency of the irradiation pulse, i is the Larmor frequency of pool i, 1 Inserting Eq. 24 into Eq.…”

Section: Appendixmentioning

confidence: 99%

“…Diamagnetic and paramagnetic chemical exchange saturation transfer (PARACEST) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(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)(14)(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)(20)(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.…”

mentioning

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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Artificial reporter gene providing MRI contrast based on proton exchange

Cited by 384 publications

References 15 publications

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

Synthetic biology devices for in vitro and in vivo diagnostics

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

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