# Tumor microenvironment-targeted theranostic paramagnetic probes

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2020 · $237,459

## Abstract

PROJECT SUMMARY/ABSTRACT 
The importance of the tumor microenvironment (TME) in tumor progression, invasion, and therapy is widely 
recognized. Intermittent and hypoxic oxygenation (pO2) and extracellular acidosis (pHe) of tumor tissues are 
among the most established hallmarks in solid TME, while extracellular inorganic phosphate (Pi) has been 
recently identified as a new signaling molecule of importance in tumorigenesis (marker of metastatic potential). 
The αvβ3 and αvβ5 integrins are usually expressed at low levels in most adult epithelia but can be highly 
upregulated in some tumors. These integrins are involved in angiogenesis and metastasis of solid tumors, and 
their inhibition resulted in significant reduction of functional vessel density, retardation of tumor growth, and 
metastasis in vivo. In this project we propose to develop theranostic multifunctional paramagnetic trityl probes 
for in vivo monitoring of basic physiological parameters (pO2, pH, Pi) using electron paramagnetic resonance- 
based techniques and patient-derived tumor xenograft (PDX) models. Specific Aim 1: Trityl probes will be 
designed to have minimal toxicity, a wide range of retention times, and antiangiogenic therapeutic effects due to 
high affinity of the probes to the αvβ3 integrins in tumor tissue. Specific Aim 2: Functional sensitivity, specific 
affinity to the αvβ3 integrin in in vitro (U87MG cells), in vivo toxicity, and targeting efficacy will be studied using a 
U87MG xenograft mouse model. Specific Aim 3. The best probe formulations will be used to construct a real- 
time TME profile during tumor development and antiangiogenic treatment using trityl probes developed in 
Specific Aim 1 and Specific Aim 2 and cilengitide (well established anti αvβ integrin drug). We hypothesize that 
the TME signature can predict levels of success for αvβ integrins based on antiangiogenic therapy. We will use 
four different cell lines which are distinctive in invasion, metastatic, and growth rate potentials, as well as 
αvβ3/αvβ5 integrin expression levels. We will perform measurements of Pi, pHe, and pO2 in tumors by L-band 
EPR. PEDRI and DCE-MRI will be used to characterize functional and spatial tumor heterogeneity. In vivo 
Electron paramagnetic resonance (EPR) Imaging, Proton electron double resonance imaging (PEDRI), and 
Dynamic contrast-enhanced (DCE)-MRI tumor characterization will be complemented with 
immunohistochemical, pathological, and biochemical tissue analysis. Successful completion of this proposed 
project will result in development of new theranostic paramagnetic multifunctional probes which can be easily 
modified with appropriate targeting motifs to study drug therapeutic effects.

## Key facts

- **NIH application ID:** 9984430
- **Project number:** 5P20GM121322-03
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Andrey Bobko
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,459
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984430

## Citation

> US National Institutes of Health, RePORTER application 9984430, Tumor microenvironment-targeted theranostic paramagnetic probes (5P20GM121322-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984430. Licensed CC0.

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