Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

Nguyen, Hung V.-T.; Detappe, Alexandre; Harvey, P. K.; Gallagher, Nolan M.; Mathieu, Cécile; Agius, Michael P.; Zavidij, Oksana; Wang, Wencong; Jiang, Yivan; Rajca, Andrzej; Jasanoff, Alan; Ghobrial, Irène M.; Ghoroghchian, P. Peter; Johnson, Jeremiah A.

doi:10.1039/d0py00558d

Cited by 23 publications

(16 citation statements)

References 86 publications

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“…However, their use is limited due to the rapid reduction reactions in vivo to diamagnetic compounds. Sterically-hindered nitroxides have much slower rates of reduction and recently were shown for such "unusual" applications as MRI [56,[69][70][71][72][73]. Nitroxide spin-labels have been classically used for two spin-labeled molecules complex investigations (distance measurement) by pulsed dipolar spectroscopy (PDS) methods of electron paramagnetic resonance (EPR), PELDOR (also known as DEER) method [43,[74][75][76][77][78].…”

Section: Homocysteine Thiolactone Building Blocks As Potential Precursors For Materials and Probesmentioning

confidence: 99%

Homocysteine Thiolactone: Biology and Chemistry

Chubarov

2021

Encyclopedia

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Homocysteine thiolactone is a five-membered cyclic thioester of amino acid homocysteine. It is generated from homocysteine as a result of an error-editing reaction, principally, of methionyl-tRNA synthetase. An elevated level of homocysteine thiolactone is associated with cardiovascular diseases, strokes, atherosclerosis, neurological abnormalities, etc., presumably because it reacts to the side chain of protein lysine causing protein damage and autoimmune responses. It is not only an important metabolite but also a versatile building block for organic and bioorganic synthesis. This entry contains data on the homocysteine thiolactone formation, metabolism, toxicity mechanism in vivo, and the bioorganic chemistry applications as a powerful synthetic tool in polymer science, sustainable materials development, and probes.

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Section: Homocysteine Thiolactone Building Blocks As Potential Precursors For Materials and Probesmentioning

confidence: 99%

Homocysteine Thiolactone: Biology and Chemistry

Chubarov

2021

Encyclopedia

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“…Nitroxyl radical labeled polymer type contrast agent for MRI called organic-radical contrast agents (ORCAs), which is structured by dendrimer core and lapping polyethylene glycol chains, has been proposed by Rajca et al [ 129 ]. For next development design of ORCA, nitroxyl radical, fluorophore, prodrug was loaded on the lapping polymer and the polymers were conjugated on core [ 130 , 131 , 132 ]. In other words, this assemble type contrast agent is working as drug carrier simultaneously, and then, monitoring of the loaded drug from the assembled compound were reported [ 132 ].…”

Section: Applications Of Redox Sensitive Nitroxyl Contrast Agents mentioning

confidence: 99%

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI, EPRI, and PET

Matsumoto¹,

Mitchell

Krishna

2021

Molecules

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Radiation therapy is one of the main modalities to treat cancer/tumor. The response to radiation therapy, however, can be influenced by physiological and/or pathological conditions in the target tissues, especially by the low partial oxygen pressure and altered redox status in cancer/tumor tissues. Visualizing such cancer/tumor patho-physiological microenvironment would be a useful not only for planning radiotherapy but also to detect cancer/tumor in an earlier stage. Tumor hypoxia could be sensed by positron emission tomography (PET), electron paramagnetic resonance (EPR) oxygen mapping, and in vivo dynamic nuclear polarization (DNP) MRI. Tissue oxygenation could be visualized on a real-time basis by blood oxygen level dependent (BOLD) and/or tissue oxygen level dependent (TOLD) MRI signal. EPR imaging (EPRI) and/or T1-weighted MRI techniques can visualize tissue redox status non-invasively based on paramagnetic and diamagnetic conversions of nitroxyl radical contrast agent. 13C-DNP MRI can visualize glycometabolism of tumor/cancer tissues. Accurate co-registration of those multimodal images could make mechanisms of drug and/or relation of resulted biological effects clear. A multimodal instrument, such as PET-MRI, may have another possibility to link multiple functions. Functional imaging techniques individually developed to date have been converged on the concept of theranostics.

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“…The results showed that the Pro‐ORCAs could serve as a valuable “reporter theranostics” for monitoring prodrug activation by MRI method (Figure 4B). [ 46 ] More importantly, this approach is realized as a general way for a range of commonly used drug delivery systems equipped with linker cleavage strategy. It is suggested that stimuli‐responsive ORCAs could afford non‐invasively reporting drug accumulation, releasing, and activation, thereby enabling real‐time and in‐time therapeutic planning.…”

Section: Monitoring Drug Fatementioning

confidence: 99%

Imaging Beyond Seeing: Early Prognosis of Cancer Treatment

et al. 2020

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Assessing cancer response to therapeutic interventions has been realized as an important course to early predict curative efficacy and treatment outcomes due to tumor heterogeneity. Compared to the traditional invasive tissue biopsy method, molecular imaging techniques have fundamentally revolutionized the ability to evaluate cancer response in a spatiotemporal manner. The past few years has witnessed a paradigm shift on the efforts from manufacturing functional molecular imaging probes for seeing a tumor to a vantage stage of interpreting the tumor response during different treatments. This review is to stand by the current development of advanced imaging technologies aiming to predict the treatment response in cancer therapy. Special interest is placed on the systems that are able to provide rapid and noninvasive assessment of pharmacokinetic drug fates (e.g., drug distribution, release, and activation) and tumor microenvironment heterogeneity (e.g., tumor cells, macrophages, dendritic cells (DCs), T cells, and inflammatory cells). The current status, practical significance, and future challenges of the emerging artificial intelligence (AI) technology and machine learning in the applications of medical imaging fields is overviewed. Ultimately, the authors hope that this review is timely to spur research interest in molecular imaging and precision medicine.

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Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

Abstract:
Pro-organic radical contrast agents (pro-ORCAs) that enable real-time monitoring of doxorubicin prodrug activation in vitro and in vivo are prepared through brush-first ring-opening metathesis polymerization (ROMP).

Cited by 23 publications

References 86 publications

Homocysteine Thiolactone: Biology and Chemistry

Homocysteine Thiolactone: Biology and Chemistry

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI, EPRI, and PET

Imaging Beyond Seeing: Early Prognosis of Cancer Treatment

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Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

Abstract: Pro-organic radical contrast agents (pro-ORCAs) that enable real-time monitoring of doxorubicin prodrug activation in vitro and in vivo are prepared through brush-first ring-opening metathesis polymerization (ROMP).

Cited by 23 publications

References 86 publications

Homocysteine Thiolactone: Biology and Chemistry

Homocysteine Thiolactone: Biology and Chemistry

Multimodal Functional Imaging for Cancer/Tumor Microenvironments Based on MRI, EPRI, and PET

Imaging Beyond Seeing: Early Prognosis of Cancer Treatment

Contact Info

Product

Resources

About

Abstract:
Pro-organic radical contrast agents (pro-ORCAs) that enable real-time monitoring of doxorubicin prodrug activation in vitro and in vivo are prepared through brush-first ring-opening metathesis polymerization (ROMP).