Mapping vitamin B<sub>6</sub> metabolism by hydrazoCEST magnetic resonance imaging

Brun, Emilie Marie Sophie Patit-Tha; Calvert, Nicholas; Suchý, Mojmı́r; Kirby, Alexia; Melkus, Gerd; Garipov, Ruslan; Addison, Christina L.; Shuhendler, Adam J.

doi:10.1039/d1cc03704h

Cited by 7 publications

(9 citation statements)

References 21 publications

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“…The high concentration of allysine during fibrogenesis makes it amenable to detection by a targeted magnetic resonance (MR) probe molecule 12,[23][24][25][26] . The general absence of aldehydes in the ECM of healthy tissue suggests that an extracellular, aldehyde-targeted probe would have high specificity for fibroproliferative disease activity.…”

Section: Mainmentioning

confidence: 99%

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

Zhou

Chen

et al. 2023

Preprint

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During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small molecule magnetic resonance (MR) probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis noninvasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, make them strong candidates for clinical translation.

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Section: Mainmentioning

confidence: 99%

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

Zhou

Chen

et al. 2023

Preprint

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“…It is also possible to derivatize the anthranilates and still retain large chemical shifts on the labile protons, with hydrazo-CEST probes being one example. 59,60 Acetanilides are similar compounds, which form intermolecular hydrogen bonds, resulting in well tuned k ex . 61 Since the labile protons resonate more than 4 ppm from water, there is minimal overlap with endogenous CEST agents, which should maximize the potential for quantification.…”

Section: Salicylates Anthranilates and Analogsmentioning

confidence: 99%

“…We have characterized a number of these compounds, which possess labile protons with chemical shifts between 5 and 12 ppm from water, including the ones shown in Figure 2, and with chemical exchange rates ( k ex ) = 100–5000 s −1 , allowing outstanding detection sensitivity for a variety of magnetic field strengths. It is also possible to derivatize the anthranilates and still retain large chemical shifts on the labile protons, with hydrazo‐CEST probes being one example 59,60 . Acetanilides are similar compounds, which form intermolecular hydrogen bonds, resulting in well tuned k ex 61 .…”

Section: Small Moleculesmentioning

confidence: 99%

A snapshot of the vast array of diamagnetic CEST MRI contrast agents

et al. 2022

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Since the inception of CEST MRI in the 1990s, a number of compounds have been identified as suitable for generating contrast, including paramagnetic lanthanide complexes, hyperpolarized atom cages and, most interesting, diamagnetic compounds. In the past two decades, there has been a major emphasis in this field on the identification and application of diamagnetic compounds that have suitable biosafety profiles for usage in medical applications. Even in the past five years there has been a tremendous growth in their numbers, with more and more emphasis being placed on finding those that can be ultimately used for patient studies on clinical 3 T scanners. At this point, a number of endogenous compounds present in tissue have been identified, and also natural and synthetic organic compounds that can be administered to highlight pathology via CEST imaging. Here we will provide a very extensive snapshot of the types of diamagnetic compound that can generate CEST MRI contrast, together with guidance on their utility on typical preclinical and clinical scanners and a review of the applications that might benefit the most from this new technology.

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“…Formimidoyltransferase cyclodeaminase (FTCD) is an enzyme that uses THF as a cofactor to perform histidine catabolism. In the presence of histidine supplementation, available pools of THF were redirected to the histidine catabolic pathway, increasing the sensitivity of cells to MTX and reducing its toxicity [ 227 , 228 ]. This landmark discovery highlights the fundamental importance of environment folate sources to antifolate therapies and provides mechanistic insight into improving therapeutic conditions.…”

Section: Exploiting One Carbon Metabolism For New Therapeuticsmentioning

confidence: 99%

Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond

et al. 2022

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Vitamin B micronutrients are essential regulators of one carbon metabolism that ensures human health. Vitamin B9, or folate, lies at the heart of the folate cycle and converges with the methionine cycle to complete the one carbon pathway. Additionally, vitamin B6 contributes by orchestrating the flux of one carbon cycling. Dysregulation of vitamin B contributes to altered biochemical signaling that manifests in a spectrum of human diseases. This review presents an analysis of the past, present, and future work, highlighting the interplay between folate and vitamin B6 in one carbon metabolism. Emerging insights include advances in metabolomic-based mass spectrometry and the use of live-cell metabolic labeling. Cancer is used as a focal point to dissect vitamin crosstalk and highlight new insights into the roles of folate and vitamin B6 in metabolic control. This collection of vitamin-based research detailing the trends of one carbon metabolism in human disease exemplifies how the future of personalized medicine could unfold using this new base of knowledge and ultimately provide next-generation therapeutics.

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Mapping vitamin B₆ metabolism by hydrazoCEST magnetic resonance imaging

Abstract: A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5’-phosphate, a key Vitamin B6 metabolite necessary for > 140 biotransformations was mapped by CEST-MRI in...

Cited by 7 publications

References 21 publications

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

A snapshot of the vast array of diamagnetic CEST MRI contrast agents

Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond

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Mapping vitamin B6 metabolism by hydrazoCEST magnetic resonance imaging

Abstract: A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5’-phosphate, a key Vitamin B6 metabolite necessary for > 140 biotransformations was mapped by CEST-MRI in...

Cited by 7 publications

References 21 publications

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

A snapshot of the vast array of diamagnetic CEST MRI contrast agents

Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond

Contact Info

Product

Resources

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Mapping vitamin B₆ metabolism by hydrazoCEST magnetic resonance imaging