# Imaging and theranostics to detect and promote an immune reactive tumor microenvironment

> **NIH NIH P41** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $267,481

## Abstract

Our purpose in TR&D1 is to develop and validate novel translatable molecular imaging and theranostic agents
to detect and promote an immune reactive tumor microenvironment (TME) that will be integrated into the
research of multiple collaborative and service projects. Immune checkpoint inhibitors have provided some of the
most exciting treatment outcomes for some cancers, but for nearly 80% of cancers the promise of cancer
immunotherapy (CIT) has not been realized. Cancers have complex TMEs with an altered extracellular matrix,
hypoxia and acidic extracelluar pH (pHe) that present a formidable barrier to immune cell infiltration and cancer
cell killing. Non-invasive translatable imaging methods that provide spatio-temporal information on mechanisms
that create barriers to CIT and provide novel theranostic strategies to improve the outcome of CIT are urgently
needed to accelerate progress in this field. During the previous funding period we have made significant
advances in multimodal imaging of the TME and siRNA theranostics that we have built upon and combined with
our expertise in PET/MR imaging, chemical exchange saturation transfer (CEST), theranostics and CIT to design
three aims that will identify a TME hostile to CIT, and provide novel theranostic approaches to overcome such
an environment to facilitate CIT. We have focused on breast and pancreatic preclinical cancer models in these
studies as these cancers have limited response to CIT. In Aim 1 we will develop novel PET and CEST MRI
probes based on decorin to expand our understand of the spatio-temporal dynamics between collagen 1,
decorin, hypoxia, pHe, and immune checkpoint PD-L1/PD-1 expression in syngeneic models of pancreatic and
breast cancer using multimodal imaging. In Aim 2 we will develop and validate multi-modality
imaging/multiplexed siRNA theranostics of myeloid derived suppressor cells (MDSCs) in the spleen and tumor
to create an immune reactive TME in these tumor models. In Aim 3 we will develop hypoxia targeted NPs to
deliver siRNA or PX-478 to downregulate HIF-1 in tumors to understand the effects of HIF-1 downregulation
on PD-L1/PD-1 expression. The reagents and resources developed in the three aims will be incorporated in a
push pull mechanism by the CPs and by the SPs to collectively advance progress in CIT.

## Key facts

- **NIH application ID:** 10848983
- **Project number:** 2P41EB024495-06A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Zaver M. Bhujwalla
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $267,481
- **Award type:** 2
- **Project period:** 2017-09-15 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848983

## Citation

> US National Institutes of Health, RePORTER application 10848983, Imaging and theranostics to detect and promote an immune reactive tumor microenvironment (2P41EB024495-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848983. Licensed CC0.

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