Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging

Elevated extracellular potassium (K<sup>+</sup>) in the tumor microenvironment (TME) of breast and other cancers is increasingly recognized as a critical factor influencing tumor progression and immune suppression. Current methods for noninvasive mapping of the potassium distribution in...

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Main Authors: Jeff Folz, Ahmad Eido, Maria E. Gonzalez, Roberta Caruso, Xueding Wang, Celina G. Kleer, Janggun Jo
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Sensors
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Online Access:https://www.mdpi.com/1424-8220/25/15/4724
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author Jeff Folz
Ahmad Eido
Maria E. Gonzalez
Roberta Caruso
Xueding Wang
Celina G. Kleer
Janggun Jo
author_facet Jeff Folz
Ahmad Eido
Maria E. Gonzalez
Roberta Caruso
Xueding Wang
Celina G. Kleer
Janggun Jo
author_sort Jeff Folz
collection DOAJ
description Elevated extracellular potassium (K<sup>+</sup>) in the tumor microenvironment (TME) of breast and other cancers is increasingly recognized as a critical factor influencing tumor progression and immune suppression. Current methods for noninvasive mapping of the potassium distribution in tumors are limited. Here, we employed photoacoustic chemical imaging (PACI) with a solvatochromic dye-based, potassium-sensitive nanoprobe (SDKNP) to quantitatively visualize extracellular potassium levels in an orthotopic metaplastic breast cancer mouse model, Ccn6-KO. Tumors of three distinct sizes (5 mm, 10 mm, and 20 mm) were imaged using multi-wavelength photoacoustic imaging at five laser wavelengths (560, 576, 584, 605, and 625 nm). Potassium concentration maps derived from spectral unmixing of the photoacoustic images at the five laser wavelengths revealed significantly increased potassium levels in larger tumors, confirmed independently by inductively coupled plasma mass spectrometry (ICP-MS). The PACI results matched ICP-MS measurements, validating PACI as a robust, noninvasive imaging modality for potassium mapping in tumors <i>in vivo</i>. This work establishes PACI as a promising tool for studying the chemical properties of the TME and provides a foundation for future studies evaluating the immunotherapy response through ionic biomarker imaging.
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spelling doaj-art-47c4ec98a25c450d8bddc6b2dcd233872025-08-20T03:36:23ZengMDPI AGSensors1424-82202025-07-012515472410.3390/s25154724Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic ImagingJeff Folz0Ahmad Eido1Maria E. Gonzalez2Roberta Caruso3Xueding Wang4Celina G. Kleer5Janggun Jo6Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USAElevated extracellular potassium (K<sup>+</sup>) in the tumor microenvironment (TME) of breast and other cancers is increasingly recognized as a critical factor influencing tumor progression and immune suppression. Current methods for noninvasive mapping of the potassium distribution in tumors are limited. Here, we employed photoacoustic chemical imaging (PACI) with a solvatochromic dye-based, potassium-sensitive nanoprobe (SDKNP) to quantitatively visualize extracellular potassium levels in an orthotopic metaplastic breast cancer mouse model, Ccn6-KO. Tumors of three distinct sizes (5 mm, 10 mm, and 20 mm) were imaged using multi-wavelength photoacoustic imaging at five laser wavelengths (560, 576, 584, 605, and 625 nm). Potassium concentration maps derived from spectral unmixing of the photoacoustic images at the five laser wavelengths revealed significantly increased potassium levels in larger tumors, confirmed independently by inductively coupled plasma mass spectrometry (ICP-MS). The PACI results matched ICP-MS measurements, validating PACI as a robust, noninvasive imaging modality for potassium mapping in tumors <i>in vivo</i>. This work establishes PACI as a promising tool for studying the chemical properties of the TME and provides a foundation for future studies evaluating the immunotherapy response through ionic biomarker imaging.https://www.mdpi.com/1424-8220/25/15/4724photoacousticchemical imagingbreast cancerCCN6metaplastic breast carcinomananoparticle
spellingShingle Jeff Folz
Ahmad Eido
Maria E. Gonzalez
Roberta Caruso
Xueding Wang
Celina G. Kleer
Janggun Jo
Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
Sensors
photoacoustic
chemical imaging
breast cancer
CCN6
metaplastic breast carcinoma
nanoparticle
title Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
title_full Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
title_fullStr Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
title_full_unstemmed Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
title_short Noninvasive Mapping of Extracellular Potassium in Breast Tumors via Multi-Wavelength Photoacoustic Imaging
title_sort noninvasive mapping of extracellular potassium in breast tumors via multi wavelength photoacoustic imaging
topic photoacoustic
chemical imaging
breast cancer
CCN6
metaplastic breast carcinoma
nanoparticle
url https://www.mdpi.com/1424-8220/25/15/4724
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