# Molecular Imaging and Theranostics of Cancer

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2021 · $982,256

## Abstract

Achieving cancer cure, or even control, continues to be a major unanswered challenge in health care despite
the remarkable technological advances of the 21st century. Advances in multi-modal noninvasive molecular
and functional imaging are providing unique opportunities to expand our understanding of cancer, an
understanding that is critical to developing effective and cancer specific treatments. In this resubmission I
have chosen three interactive focus areas within the tumor microenvironment (TME), the tumor
macroenvironment (TMacE), and Theranostics, that will be pursued in triple negative breast cancer (TNBC)
and pancreatic ductal adenocarcinoma (PDAC) human tumor xenografts and syngeneic tumors in immune
competent mice. In the TME focus, we will use imaging to expand our understanding of the focal adhesion
kinase (FAK) mechanotransduction pathway in the metastatic cascade that will include developing PET
imaging probes to detect FAK noninvasively. FAK also plays a role in tumor immune suppression. In the
TMacE focus we will expand our efforts in understanding PDAC induced cachexia that results in a wide range
of symptoms affecting the function of organs such as muscle, liver, brain, and heart, causing significant
morbidity. The tumor secretome holds the key to this syndrome by influencing the `macroenvironment'. We
will focus on characterizing the tumor interstitial fluid (TIF) in preclinical PDAC xenograft models to develop
biomarkers of cachexia and identify potential metabolic targets that will be pursued through the Theranostic
focus. In the Theranostic focus we will direct our efforts and expertise in imaging and NP technology to
improve the outcome of checkpoint inhibitors in TNBC and PDAC. Lack of effector T-cell tumor infiltration has
been identified as a major cause of the poor response to these inhibitors. We will use FDA approved
poly(lactic-co-glycolic acid) PLGA to create cancer cell membrane (CCM) coated `immunosome' NPs
embedded with granulocyte macrophage colony-stimulating factor (GM-CSF) to increase effector T cell tumor
infiltration, and apply molecular imaging to detect the biodistribution of the NPs and the changes in T cell
infiltration. Ultimately we want to use the patients own cancer cells to synthesize the NPs for personalized
medicine. Since FAP-α expressing cancer associated fibroblasts (CAFs) are known to create an immune
suppressive TME, we will use anti-FAP-α antibody conjugated to the near infrared (NIR) dye IR700 to detect
CAFS with NIR imaging and eliminate them selectively in the tumor with PIT. If PIT of FAP-α expressing CAFs
results in increased cytotoxic T cells in tumors, this may have significant applications in combination with
checkpoint inhibitor treatment. We will use siRNA delivery with dextran based biocompatible NPs to
downregulate FAK, and metabolic targets identified in the TMacE focus. I have built a strong network of
collaborators that include clinical oncologists, radiologists, pathologists...

## Key facts

- **NIH application ID:** 10242814
- **Project number:** 5R35CA209960-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Zaver M. Bhujwalla
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $982,256
- **Award type:** 5
- **Project period:** 2017-09-04 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242814

## Citation

> US National Institutes of Health, RePORTER application 10242814, Molecular Imaging and Theranostics of Cancer (5R35CA209960-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242814. Licensed CC0.

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