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bioRxiv · 10.1101/2023.05.18.541366

Evaluation of a deuterated triarylmethyl spin probe for in vivo R2*-based EPR oximetric imaging with enhanced dynamic range

Kishimoto, S.·Devasahayam, N.·Chandramouli, G. V.·Murugesan, R.·Otowa, Y.·Yamashita, K.·Yamamoto, K.·Brender, J. R.·Krishna, M. C.
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Abstract

PurposeIn this study, we compared two triarylmethyl (TAM) spin probes, Ox071 and Ox063 for their efficacy in measuring tissue oxygen concentration by R2*-based oximetry in hypoxic and normoxic conditions. MethodsThe R2* dependence with spin probe and oxygen was calibrated using standard phantom solutions at 1, 2, 5, 10 mM spin probe and 0, 2, 5, 10, 21% oxygen concentrations. For a hypoxic model, in vivo imaging of a MIA PaCa-2 tumor implanted in the hind leg of a mouse was performed on successive days by using either Ox071 or Ox063. For normoxic model, renal imaging of healthy athymic mice was performed under similar conditions. The 3D spin density images acquired under three different gradients and reconstructed by single point imaging modality were used for computing the R2 * values. ResultsThe signal intensities of Ox071 were about three times greater in the phantom solutions than Ox063 in the entire pO2 range investigated. Although histograms computed from the pO2 images of the tumor were skewed towards low pO2 levels for both spin probes due to R2* signal loss, more frequency counts in the normoxic region at pO2 > 32 mmHg could be detected with Ox071. In the normoxic model in kidney, the high pO2 cortex and the low pO2 medulla regions were well delineated. The histograms of high-resolution kidney oximetry images using Ox071 were nearly symmetrical and frequency counts were seen up to 55 mmHg which were missed in Ox063 imaging. ConclusionThis study illustrates Ox071 as a better oximetric probe than Ox063 in terms of sensitivity and the pO2 dynamic range.

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Kishimoto, S., Devasahayam, N., Chandramouli, G. V., Murugesan, R., Otowa, Y., Yamashita, K., Yamamoto, K., Brender, J. R., Krishna, M. C.. 2023-05-18. Evaluation of a deuterated triarylmethyl spin probe for in vivo R2*-based EPR oximetric imaging with enhanced dynamic range. https://doi.org/10.1101/2023.05.18.541366

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