# Personalized Cancer Therapy Guided by Photoacoustic Chemical Imaging (PACI) of Tumor Microenvironment (TME)

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $625,319

## Abstract

Title: Personalized Cancer Therapy Guided by Photoacoustic Chemical Imaging (PACI)
of Tumor Microenvironment (TME)
Abstract:
Tumors are often found in an altered metabolic state, which leads to anomalous chemical composition, such as
hypoxia (low oxygen level), acidosis (low pH level), and hyperkalemia (high potassium concentration). These
three form a “therapy resistance triad (O2, pH, and K+)”, suppressing cancer’s responses to radio-, chemo-,
and immuno-therapy. As each triad member’s concentration is strongly relevant to cancer progress and
response to therapy, a non-invasive, sensitive, and reliable approach for evaluating their temporal and spatial
distributions in the tumor microenvironment (TME) in vivo, non-invasively, is highly desirable. To fill this serious
and long-standing gap in technology, we introduce a novel set of O2, pH, and K+ sensing nanoprobes that, in
combination with the emerging photoacoustic imaging technology, enables quantitative mapping of the O2, pH,
and K+ levels in solid tumors in vivo. The central hypothesis of this proposed research is that, enabled by our
photoacoustic chemical imaging (PACI) powered with sensitive chemical indicator nanoprobes, we can image
and quantitatively evaluate the spatio-temporal distributions of the TME’s therapy resistance triad (O2, pH, and
K+), at depths of up to a few centimeters, in vivo and in a non-invasive fashion, and then correlate with cancer
responses to treatments via radio-, chemo-, and immuno-therapy. This hypothesis will be examined rigorously
using orthotopic patient derived xenograft (PDX) breast cancer mouse models. To enable a comprehensive
understanding of the technology’s capabilities, as well as limitations, the imaging results from PACI of the TME
will be compared for a wide variety of PDX tumor models and treatment situations. To examine the central
hypothesis, our research will focus on three specific aims: Aim 1. Understand tumor response to radio-therapy
by PACI of the TME; Aim 2. Understand tumor response to chemo-therapy by PACI of the TME; and Aim 3.
Understand tumor response to immuno-therapy by PACI of the TME.
Potential impact: As the orthotopic PDX tumors faithfully resemble the original tumors in cancer patients,
including their TME, chemical imaging of these PDX tumors, combined with studying the correlations of the
imaging findings with the cancer responses to therapies, could have a large impact on translational research
and clinical management of breast cancer, e.g. helping to discriminate the most suitable treatment plan or
alternative plan for individual cancer patients. By the end of this funding period, we will objectively test and
thoroughly verify whether the novel PACI technology powered by sensitive nanoprobes can image the TME’s
chemical properties of PDX mouse tumors in vivo, non-invasively, for predicting the cancer responses to radio-
, chemo-, and immuno-therapy. Once successfully validated, the proposed strategy could shed new ligh...

## Key facts

- **NIH application ID:** 10072115
- **Project number:** 1R01CA250499-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Raoul Kopelman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $625,319
- **Award type:** 1
- **Project period:** 2020-06-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072115

## Citation

> US National Institutes of Health, RePORTER application 10072115, Personalized Cancer Therapy Guided by Photoacoustic Chemical Imaging (PACI) of Tumor Microenvironment (TME) (1R01CA250499-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072115. Licensed CC0.

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