In vivo quantitative imaging of tumor pH by nanosonophore assisted multispectral photoacoustic imaging

Janggun Jo,Raoul Kopelman,Xueding Wang,Chang H Lee

doi:10.1038/s41467-017-00598-1

Janggun Jo, Raoul Kopelman + Show 2 more

Open Access

https://doi.org/10.1038/s41467-017-00598-1

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Journal: Nature Communications	Publication Date: Sep 7, 2017
Citations: 101	License type: open-access

Affiliation: University of Michigan–Ann Arbor

Abstract

Changes of physiological pH are correlated with several pathologies, therefore the development of more effective medical pH imaging methods is of paramount importance. Here, we report on an in vivo pH mapping nanotechnology. This subsurface chemical imaging is based on tumor-targeted, pH sensing nanoprobes and multi-wavelength photoacoustic imaging (PAI). The nanotechnology consists of an optical pH indicator, SNARF-5F, 5-(and-6)-Carboxylic Acid, encapsulated into polyacrylamide nanoparticles with surface modification for tumor targeting. Facilitated by multi-wavelength PAI plus a spectral unmixing technique, the accuracy of pH measurement inside the biological environment is not susceptible to the background optical absorption of biomolecules, i.e., hemoglobins. As a result, both the pH levels and the hemodynamic properties across the entire tumor can be quantitatively evaluated with high sensitivity and high spatial resolution in in vivo cancer models. The imaging technology reported here holds the potential for both research on and clinical management of a variety of cancers.

Highlights

Changes of physiological pH are correlated with several pathologies, the development of more effective medical pH imaging methods is of paramount importance
As shown in the normalized optical absorption spectra (Fig. 1a), measured by an ultraviolet–visible (UV–VIS) spectrometer, the spectroscopic absorption of SNARF-5F 5-(and-6)-carboxylic acid (SNARF)-PAA NPs varies with the pH level
We presented a NP assisted, non-invasive, in vivo photoacoustic imaging (PAI) technique for quantitative pH imaging of subsurface solid tumors in vivo based on optical spectroscopy

Summary

Introduction

Changes of physiological pH are correlated with several pathologies, the development of more effective medical pH imaging methods is of paramount importance. Facilitated by multi-wavelength PAI plus a spectral unmixing technique, the accuracy of pH measurement inside the biological environment is not susceptible to the background optical absorption of biomolecules, i.e., hemoglobins As a result, both the pH levels and the hemodynamic properties across the entire tumor can be quantitatively evaluated with high sensitivity and high spatial resolution in in vivo cancer models. As a result of the strong optical scattering of biological tissues, traditional optical spectroscopy is not able to achieve satisfactory spatial resolution when the target tissue is beyond the sample surface This limited spatial resolution in imaging subsurface tumor inevitably leads to limited accuracy in evaluating the cancer microenvironment, because the functional hallmarks of tumor including the acidosis show strong heterogeneity.

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