Singlet Oxygen-Responsive MRI Contrast Agents
Abstract
In vivo imaging detection of singlet oxygen (1O2) produced by photodynamic therapy remains a challenge. To address this unmet necessity, two Gd3+-based multicyclic magnetic resonance imaging (MRI) probes 1 and 2 were synthesized and characterized for their ability to react with 1O2 and for their relaxivity, r1, enhancement. We employed a chemical design based on capping the Gd-DOTA-chelate with two differently sized aromatic bridging moieties, benzene for 1 and naphthalene for 2, connected with secondary amine linkers. Upon exposure to 1O2, probes 1 and 2 underwent an uncapping transformation by oxidative cleavage of the benzyl/naphthylmethyl amine linker, resulting in an open form, probe 3, with r1 relaxivity changes corresponding to a 31% decrease or a 19% increase, respectively. To understand these r1 values, probes 1 and 2 were further characterized by relaxometric measurements at variable temperature and pH and 17O NMR, along with 1H NMR and luminescence of analogous Eu3+-complexes, suggesting that these relaxivity variations were the result of a complex interplay between several different factors, including the effect of second-sphere water. DFT calculations supported that probes 1–3 retain a single inner-sphere water molecule, indicating that the experimentally observed relaxivity differences did not arise from the change of coordination number but rather from steric shielding by the aromatic moiety which affects various interactions contributing to relaxivity. These results provide a mechanistic proof-of-concept and demonstrate that the oxidative cleavage of arylamines by 1O2 can promote relaxivity variations in Gd3+-complexes, representing a distinct strategy for the design of 1O2-responsive MRI contrast agents.
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BibTeX
@article{staudhammer2026singlet,
title = {{Singlet Oxygen-Responsive MRI Contrast Agents}},
author = {Sara Staudhammer and Agnès Pallier and Hikari Yoshihara and Olga Stasyuk and Aurélien Bornet and Marc-Eduard Usteri and Lorenzo Persi and Miquel Solà and Daniel Razansky and Éva Tóth and Yoko Yamakoshi},
journal = {Chemical \& Biomedical Imaging},
year = {2026},
month = oct,
doi = {10.1021/cbmi.6c00150},
url = {https://hal.science/hal-05843466v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Singlet Oxygen-Responsive MRI Contrast Agents
AU - Sara Staudhammer
AU - Agnès Pallier
AU - Hikari Yoshihara
AU - Olga Stasyuk
AU - Aurélien Bornet
AU - Marc-Eduard Usteri
AU - Lorenzo Persi
AU - Miquel Solà
AU - Daniel Razansky
AU - Éva Tóth
AU - Yoko Yamakoshi
PY - 2026
DA - 2026/10/03
JO - Chemical & Biomedical Imaging
DO - 10.1021/cbmi.6c00150
UR - https://hal.science/hal-05843466v1
AB - In vivo imaging detection of singlet oxygen (1O2) produced by photodynamic therapy remains a challenge. To address this unmet necessity, two Gd3+-based multicyclic magnetic resonance imaging (MRI) probes 1 and 2 were synthesized and characterized for their ability to react with 1O2 and for their relaxivity, r1, enhancement. We employed a chemical design based on capping the Gd-DOTA-chelate with two differently sized aromatic bridging moieties, benzene for 1 and naphthalene for 2, connected with secondary amine linkers. Upon exposure to 1O2, probes 1 and 2 underwent an uncapping transformation by oxidative cleavage of the benzyl/naphthylmethyl amine linker, resulting in an open form, probe 3, with r1 relaxivity changes corresponding to a 31% decrease or a 19% increase, respectively. To understand these r1 values, probes 1 and 2 were further characterized by relaxometric measurements at variable temperature and pH and 17O NMR, along with 1H NMR and luminescence of analogous Eu3+-complexes, suggesting that these relaxivity variations were the result of a complex interplay between several different factors, including the effect of second-sphere water. DFT calculations supported that probes 1–3 retain a single inner-sphere water molecule, indicating that the experimentally observed relaxivity differences did not arise from the change of coordination number but rather from steric shielding by the aromatic moiety which affects various interactions contributing to relaxivity. These results provide a mechanistic proof-of-concept and demonstrate that the oxidative cleavage of arylamines by 1O2 can promote relaxivity variations in Gd3+-complexes, representing a distinct strategy for the design of 1O2-responsive MRI contrast agents.
SN - 2832-3637
ER -