Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Xiaoxiao Zhang, Yaping Yuan, Sha Li, Qingbin Zeng, Qianni Guo, Na Liu, Minghui Yang, Yunhuang Yang, Maili Liu, Michael T Mcmahon, Xin Zhou

Research output: Contribution to journalArticle

Abstract

Purpose: CEST 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. Methods: To 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. Results: Based 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. Conclusion: These 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.

Original languageEnglish (US)
Pages (from-to)577-585
Number of pages9
JournalMagnetic resonance in medicine
Volume82
Issue number2
DOIs
StatePublished - Aug 1 2019

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Porphyrins
Contrast Media
Protons
Water
Neoplasm Grading
Nitrogen
Technology
Research
chlorin
Neoplasms

Keywords

  • CEST imaging
  • contrast agents
  • free-base porphyrin
  • molecular imaging
  • upfield-shifted protons

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons. / Zhang, Xiaoxiao; Yuan, Yaping; Li, Sha; Zeng, Qingbin; Guo, Qianni; Liu, Na; Yang, Minghui; Yang, Yunhuang; Liu, Maili; Mcmahon, Michael T; Zhou, Xin.

In: Magnetic resonance in medicine, Vol. 82, No. 2, 01.08.2019, p. 577-585.

Research output: Contribution to journalArticle

Zhang, X, Yuan, Y, Li, S, Zeng, Q, Guo, Q, Liu, N, Yang, M, Yang, Y, Liu, M, Mcmahon, MT & Zhou, X 2019, 'Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons', Magnetic resonance in medicine, vol. 82, no. 2, pp. 577-585. https://doi.org/10.1002/mrm.27753
Zhang, Xiaoxiao ; Yuan, Yaping ; Li, Sha ; Zeng, Qingbin ; Guo, Qianni ; Liu, Na ; Yang, Minghui ; Yang, Yunhuang ; Liu, Maili ; Mcmahon, Michael T ; Zhou, Xin. / Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons. In: Magnetic resonance in medicine. 2019 ; Vol. 82, No. 2. pp. 577-585.
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AU - Zhang, Xiaoxiao

AU - Yuan, Yaping

AU - Li, Sha

AU - Zeng, Qingbin

AU - Guo, Qianni

AU - Liu, Na

AU - Yang, Minghui

AU - Yang, Yunhuang

AU - Liu, Maili

AU - Mcmahon, Michael T

AU - Zhou, Xin

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N2 - Purpose: CEST 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. Methods: To 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. Results: Based 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. Conclusion: These 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.

AB - Purpose: CEST 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. Methods: To 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. Results: Based 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. Conclusion: These 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.

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