APM OpenIR
Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons
Zhang, Xiaoxiao1; Yuan, Yaping1,2; Li, Sha1,2; Zeng, Qingbin1,2; Guo, Qianni1,2; Liu, Na1,2; Yang, Minghui1,2; Yang, Yunhuang1,2; Liu, Maili1,2; McMahon, Michael T.3,4; Zhou, Xin1,2
2019-08-01
Source PublicationMAGNETIC RESONANCE IN MEDICINE
ISSN0740-3194
Volume82Issue:2Pages:577-585
AbstractPurposeCEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free-base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection. MethodsTo test these newly identified CEST agents, we acquired a series of Z-spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor-bearing mice, and MR images were acquired to assess detection feasibility in vivo. ResultsBased on the Z-spectra, the inner nitrogen protons in free-base porphyrins and chlorin resonate from -8 to -13.5 ppm from water, far shifted from the majority of endogenous metabolites (0-4 ppm) and Nuclear Overhauser enhancements (-1 to -3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5-12 ppm). The exchange rates are sufficiently slow to intermediate (500-9000 s(-1)) to allow robust detection and were sensitive to substituents on the porphyrin ring. ConclusionThese results highlight the capabilities of free-base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications.
KeywordCEST imaging contrast agents free-base porphyrin upfield-shifted protons molecular imaging
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health
DOI10.1002/mrm.27753
WOS KeywordIN-VIVO ; MAGNETIC-RESONANCE ; NONINVASIVE DETECTION ; SALICYLIC-ACID ; SATURATION ; EXPRESSION ; COMPLEXES ; IOPAMIDOL ; SPECTRA ; GLUCOSE
Language英语
Funding ProjectNational Natural Science Foundation of China[81625011] ; National Natural Science Foundation of China[81227902] ; National Key R&D Program of China[2016YFC1304700] ; National Key R&D Program of China[2017YFA0505400] ; Key Research Program of Frontier Sciences, CAS[QYZDY-SSW-SLH018] ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health[P41EB024495]
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; Key Research Program of Frontier Sciences, CAS ; Key Research Program of Frontier Sciences, CAS ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Program for Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals) ; National Institutes of Health ; National Institutes of Health
WOS Research AreaRadiology, Nuclear Medicine & Medical Imaging
WOS SubjectRadiology, Nuclear Medicine & Medical Imaging
WOS IDWOS:000471308300006
PublisherWILEY
Citation statistics
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/14516
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorZhou, Xin
Affiliation1.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst,Wuhan Inst Phy, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Collaborat Innova, Wuhan, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol, Baltimore, MD USA
4.Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA
Recommended Citation
GB/T 7714
Zhang, Xiaoxiao,Yuan, Yaping,Li, Sha,et al. Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons[J]. MAGNETIC RESONANCE IN MEDICINE,2019,82(2):577-585.
APA Zhang, Xiaoxiao.,Yuan, Yaping.,Li, Sha.,Zeng, Qingbin.,Guo, Qianni.,...&Zhou, Xin.(2019).Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons.MAGNETIC RESONANCE IN MEDICINE,82(2),577-585.
MLA Zhang, Xiaoxiao,et al."Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons".MAGNETIC RESONANCE IN MEDICINE 82.2(2019):577-585.
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