Tracking inflammation across tissues with a targeted PET probe

Inflammation is the body’s first line of defense, rushing to fight off invaders and repair damaged cells to restore balance. But when this response is mistimed or overactive, it can backfire — fueling diseases like cancer, diabetes, stroke, or colitis. Precisely tracking and mapping inflammation could transform how clinicians diagnose, monitor, and treat these conditions.

Yet, current invasive approaches to detect inflammation can be costly and time-consuming, and existing non-invasive tools have their own limitations — some lack specificity, others fall short on sensitivity. In a recent study, researchers sought to strike a balance by designing a positron emission tomography (PET) probe that targets CD45, a protein expressed on all immune cells (1). The new probe promises a practical and precise way to visualize inflammation, potentially complementing existing methods.

Its expression increases in the setting of inflammation, so it actually offers a great profile as a universal probe to detect inflammation at the site of accumulation of immune cells.
- Ali Salehi Farid, Dana-Farber Cancer Institute and Harvard Medical School

Researchers have been working for years to develop imaging tools for inflammation. Some PET tracers, like the radiolabeled glucose analog ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), are taken up by multiple cell types. Clinicians have used ¹⁸F-FDG for decades to identify sites of inflammation and infection (2). However, because it accumulates in tissues with high glucose demand, it often fails to distinguish inflammation from other metabolic activity, increasing the risk of false positives (3). On the other extreme, researchers have developed probes that target specific immune cell subtypes, such as T cells, but this specificity limits their use to select scenarios (4).

Coauthor Ali Salehi Farid, a molecular imaging researcher at Dana-Farber Cancer Institute and Harvard Medical School, and his colleagues were looking for a tracer as universal as ¹⁸F-FDG but that would selectively target immune cells to strike a balance between specificity and versatility for diagnosing diverse inflammatory conditions. As a pan-immune cell marker, CD45 was an ideal fit. “In addition to that, its expression increases in the setting of inflammation, so it actually offers a great profile as a universal probe to detect inflammation at the site of accumulation of immune cells,” said Salehi Farid.

The team injected mice intravenously with the CD45-targeting probe which was attached to zirconium-89, a widely used PET radiometal (5). In healthy mice, Salehi Farid and his colleagues visualized immune organs like the spleen and bone marrow. The CD45-PET probe revealed bowel inflammation in a colitis mouse model. In a mouse model of acute respiratory distress syndrome (ARDS), a condition characterized by lung inflammation, the probe’s signal intensified in the affected organs. Moreover, the signal intensity correlated with markers of disease severity in this ARDS model. Repeating the process with the broad ¹⁸F-FDG probe and the specific myeloid marker CD11b-PET probe, the researchers visualized lung inflammation as well. However, those two probes failed to distinguish disease intensity.

To advance this probe toward human translation, Salehi Farid and his colleagues targeted it to human CD45 and tested it in genetically modified mice with humanized immune systems. Three weeks after the injection, the tracer successfully visualized human immune cells in the spleen. As some of the mice later developed graft-versus-host disease symptoms, the probe also detected inflammation in organs infiltrated with immune cells. Salehi Farid and other team members, listed as inventors on a patent application associated to this study, are now validating the probe in additional preclinical models and hope to secure funding for clinical translation.

Xiaoyuan (Shawn) Chen, a molecular imaging researcher at the National University of Singapore who did not participate in this work, noted that some existing biomarkers and radiological methods already provide accurate measurements to assess inflammation to some extent. “For the sake of diagnosis, [the CD45-PET probe] may just fall into the [same] category [as] many other inflammation probes,” said Chen, who also cofounded the nuclear medicine company Yantai Lannacheng Biotechnology Co., Ltd. But when combined with other imaging tools, he said that this new probe could enhance diagnostic accuracy.

Rather than a one-time image diagnostic tool, Chen said that the CD45-PET probe could be valuable for capturing multiple images before, during, and after certain interventions. For instance, he emphasized its potential for tracking conditions treated with CD45-related therapies.

Jennifer Rowley, a coauthor of the study and a molecular imaging researcher at Dana-Farber Cancer Institute and Harvard Medical School, acknowledged the probe’s limitations. “We need to be careful about not positioning CD45[-PET] as something that’s going to replace tried-and-true procedures,” she said, citing colonoscopies for diagnosing inflammatory bowel disease (IBD) as an example. But, while effective, colonoscopies don’t reach all areas of the gastrointestinal tract. Thus, Salehi Farid said that this probe could then serve as a companion tool. Moreover, once diagnosed with IBD, patients may require a surveillance colonoscopy every one to five years, depending on disease severity. In these scenarios, the CD45-PET probe could help monitor the disease progression and potentially reduce the need for some colonoscopies.

Salehi Farid also noted that some biopsies, such as liver biopsies, often yield false negatives due to limited sampling. Using the CD45-PET probe to guide these procedures could narrow down the sampling site and potentially reduce the risk of false negatives, he said.

Finally, Rowley noted that researchers developed many diagnostic tools for inflammatory conditions over a century ago. She envisions a future where physicians rely less on invasive procedures as a first-line diagnostic approach and move toward non-invasive, whole-body precision medicine. “I think that’s a really amazing paradigm shift within medicine,” she said. “I hope CD45[-PET] will be part of that push.”

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