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Noninvasive Inflammation Imaging Using a CD45-PET Probe Aids in Diagnosis and Monitoring

This innovative approach can noninvasively image inflammation within the body with high specificity, potentially transforming various aspects of inflammatory disease management.

  • Diagnostics

Project Overview

  • CD45, a member of the protein tyrosine phosphatase family, is found on the surface of all hematopoietic cells with a few exceptions.
  • Dana-Farber researchers are developing a PET-probe targeting CD45 to aid in more specific and reproducible noninvasive imaging of inflammation. 
  • The CD45-PET probe technology is available for licensing or sponsored research partnerships.

Technology

Molecular imaging with PET shows promise as a next generation diagnostic modality for immune-mediated conditions. Using targeted probes, PET noninvasively provides quantitative, whole-body visualization of functional processes or features of cells and tissues of interest. When PET probes bind their target of interest, information about the location, density, and distribution of that target is detected. However, the lack of a specific, sensitive, and reproducible PET probe to detect inflammation remains a critical challenge.  

Current PET imaging methods commonly used in diagnostic profiling, disease monitoring, and treatment response use fluorodeoxyglucose (18F-FDG), which is not target-specific, and suffers from low reproducibility.  

Dr. Mohammad Rashidian has developed an improved technology over current methods because of CD45 targeting. The approach, described in a Nature paper, uses small antibody fragments specific to human CD45 as the basis for his novel PET probe technology. CD45, also referred to as leukocyte common antigen, is exclusively expressed on all immune cells which inherently allows for substantial versatility as a diagnostic tool across a broad range of diseases.  CD45 expression remains elevated during immune activation, further ensuring its ability to detect inflammation with high sensitivity. Notably, their results show a robust correlation exists between the intensity of the CD45-PET signal and inflammation severity. 

To establish their approach, the team utilized a CD45 nanobody, the smallest naturally derived antibody fragment, to evaluate the effectiveness of CD45-PET in detecting inflammation. This strategy, which employs small antibody fragments, offers excellent tissue penetration, high target affinity, and rapid clearance from the circulation, enabling imaging the day after infusion. Their findings demonstrated that CD45-PET was highly sensitive and specific in identifying inflammation across various contexts, such as lung and colon inflammation. Additionally, they showed that CD45-PET could be used for serial imaging, allowing for the monitoring of treatment responses and assessing whether inflammation decreases following treatment. The results indicated that CD45-PET could accurately track inflammation dynamics in specific organs and outperformed 18F-FDG-PET, the current gold standard PET probe in clinical settings, in assessing disease severity.  

For clinical translation, the team developed a human CD45-PET probe. To synthesize this probe, Rashidian’s team engineered a full-size CD45 antibody, previously used in clinical radiotherapy, into a smaller antibody fragment.  With this novel human CD45-PET probe, the Rashidian lab has created the first in vivo images of the whole immune system in humanized mice, including pathogenic inflammation.

This imaging platform also provides insights into changes in the inflammatory profile of specific tissues, including cardiac tissue for indications such as sarcoidosis. CD45-PET captures and characterizes inflammatory processes that are organ-specific and whole-body, focal and diffuse, as well as acute and chronic-onset. 

Team Members: Mohammad Rashidian, PhD, Ali Salehi Farid, PharmD, Jennifer Rowley

Applications

The use of CD45-PET as an inflammation biomarker has the potential to become a standard practice in clinical settings. Offering direct visualization of immune cell infiltration, CD45 imaging can significantly assist in precise disease diagnosis, staging, and ongoing monitoring of inflammatory conditions. This valuable information can guide treatment decisions, facilitate personalized therapeutic strategies and timely interventions.  

The potential applications of this imaging approach are wide-ranging. The Rashidian team has assessed the effectiveness of CD45-PET probes in detecting inflammation, generating proof of principle data in mice on assessing inflammation in the lung (ARDS), and colon (IBD), and are exploring CD45-PET abilities to detect inflammation in other major organs like liver and heart as well as using CD45-PET for detection of early cancer metastasis. 

The team’s human CD45-PET probe efficiently detects inflammation in a humanized graft-vs-host disease mouse model, where early detection remains a pressing unmet need.  Other potential applications for CD45 imaging include inflammatory cardiomyopathies. 

Interested in learning more?

CD45-PET is a robust, non-invasive tool for imaging inflammation

2025 Nature paper

Opportunities

Dana-Farber welcomes discussions with interested parties to accelerate the development of its CD45-PET technology. 

Get in touch

Team Members