# Co-Clinical Research Resource for Imaging Tumor Associated Macrophages

> **NIH NIH U24** · STANFORD UNIVERSITY · 2023 · $639,130

## Abstract

Co-Clinical Research Resource for Imaging Tumor Associated Macrophages
ABSTRACT
The development of quantitative imaging (QI) methods for monitoring cancer therapy response has
been transformative for the development of novel cancer therapeutics. QI efforts have positioned imaging as
a key element in the design of clinical trials for cancer therapy response assessment. Hence, there is
increased interest by the academic and industry sectors to use web accessible research resources and
develop consensus approaches to validate QI methods for the next generation of clinical trials. This is
particularly relevant for assessment of cancer immunotherapy, since immunotherapy does not lead to a
decrease in tumor size, at least not in the immediate post-treatment phase. Therefore, we urgently need new
QI tools that can monitor tumor response to novel immunotherapies. The overall goal of our project is to
optimize and validate preclinical and clinical imaging techniques for in vivo quantification of tumor
associated macrophages (TAM) in osteosarcomas. Recent evidence has shown that the abundant TAM
response in the microenvironment of bone sarcomas can be employed to directly attack cancer cells.
Blockade of the cell surface molecule CD47 expressed on sarcoma cells resulted in activation of phagocytic
anti-cancer activity from TAM and efficiently eradicated tumor cells in mouse models of osteosarcoma. 26
Preclinical studies have been finalized and a multi-center phase I clinical trial is currently being planned, with
expected start date in 2021. To solve the unmet clinical need for a QI tool to monitor response to new TAM-
modulating therapies, our team developed a quantitative TAM imaging test, which relies on intravenous
injection of the iron supplement ferumoxytol. Ferumoxytol is composed of iron oxide nanoparticles, which are
phagocytosed by TAM and can be quantified with T2*-weighted MRI 45. Since ferumoxytol is FDA-approved
and can be used “off label” as a TAM biomarker, it is immediately clinically available. We showed that
ferumoxytol-MRI can detect TAM in osteosarcomas in mouse models 21 and patients 25. Through this
project, we will (a) optimize and validate pre-clinical quantitative imaging methods for TAM imaging in
an established mouse model of osteosarcoma, (b) implement the optimized methods in a co-clinical
trial in patients with osteosarcoma who are undergoing immunotherapy with CD47 mAb, and finally
(c) populate a web-accessible research resource with all the data, methods, and results collected
from the co-clinical investigations. Developing the proposed imaging test could represent a significant
breakthrough for clinicians as a new means for treatment stratification and new gold-standard imaging test for
predicting treatment response of novel immunotherapies. Our QI imaging test could be utilized to compare
the efficacy of different immune-modulating therapies in preclinical settings and translate the most primising
candidates to the clinic...

## Key facts

- **NIH application ID:** 10688045
- **Project number:** 5U24CA264298-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Heike Elizabeth Daldrup-Link
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $639,130
- **Award type:** 5
- **Project period:** 2021-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10688045

## Citation

> US National Institutes of Health, RePORTER application 10688045, Co-Clinical Research Resource for Imaging Tumor Associated Macrophages (5U24CA264298-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10688045. Licensed CC0.

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