TREM2-Targeting peptide tracer for neuroinflammation PET imaging.
A new peptide tracer just made TREM2 imaging in the brain a whole lot easier. Researchers out of ShanghaiTech University have designed a DOTA-conjugated peptide, labeled with gallium-68, that targets TREM2 — a key player in neuroinflammation and neurodegenerative disease. The compound, called [68Ga]Ga-STZL730, nails the basics: high radiochemical purity, strong stability, and specific binding to TREM2.
Eur J Nucl Med Mol Imaging
by Zhang X, Liu W, Guo N et al.
“TREM2-Targeting peptide tracer for neuroinflammation PET imaging. Zhang X(#)(1), Liu W(#)(1)(2), Guo N(#)(3)(4), Gao X(1)(5), Pu S(1)(2), Yang Y(1)(5), Zha X(1)(5), Ding K(1)(2), Shi D(6), Zhao J(7)(8), Cheng D(9)(10), Luo Z(11)(12). Author information: (1)School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, 201210, China. (2)School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, China. (3)Shanghai Institute for Advanced Immunochemical Studies & School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. (4)Shanghai Clinical Research and Trial Center, Shanghai, 201210, China. (5)School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. (6)Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. (7)Shanghai Institute for Advanced Immunochemical Studies & School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. zhaojian@shanghaitech.edu.cn. (8)Shanghai Clinical Research and Trial Center, Shanghai, 201210, China. zhaojian@shanghaitech.edu.cn. (9)School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, 201210, China. chengdf@shanghaitech.edu.cn. (10)Shanghai Clinical Research and Trial Center, Shanghai, 201210, China. chengdf@shanghaitech.edu.cn. (11)School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, 201210, China. luozh@shanghaitech.edu.cn. (12)Shanghai Clinical Research and Trial Center, Shanghai, 201210, China. luozh@shanghaitech.edu.cn. (#)Contributed equally PURPOSE: Triggering receptor expressed on myeloid cells 2 (TREM2) has emerged as an important target in neurodegenerative diseases. However, noninvasive visualization of TREM2 expression in the central nervous system (CNS) remains challenging. This study aimed to develop and evaluate a novel peptide-based positron emission tomography (PET) tracer for imaging TREM2 in CNS. METHODS: A TREM2-targeting peptide was conjugated with DOTA and radiolabeled with gallium-68 to generate [68Ga]Ga-STZL730. Binding affinity, tracer stability, lipophilicity, and cellular uptake were evaluated. Dynamic PET imaging and blocking studies were performed in wild-type mice, TREM2 knockout mice, lipopolysaccharide (LPS)-induced neuroinflammation mice, and APP/PS1 Alzheimer's disease (AD) model mice. Autoradiography and immunofluorescence staining were conducted to validate tracer specificity and target expression. RESULTS: [68Ga]Ga-STZL730 was synthesized with high radiochemical purity (> 99%) and demonstrated excellent stability in vitro. The tracer exhibited specific binding to TREM2 with an affinity (KD) of 274 nM. In vivo PET imaging demonstrated that [68Ga]Ga-STZL730 could cross the blood-brain barrier, displaying moderate and sustained brain uptake. Notably, at 20-35 min post-injection, compared to wild-type controls, brain uptake was significantly reduced in TREM2 knockout mice (41.6% lower), whereas it was markedly increased in both LPS-treated mice (113.8% higher) and AD mice (86.0% higher). Blocking studies in AD mice demonstrated the specific binding of [68Ga]Ga-STZL730. In vitro autoradiography and immunohistochemical analyses further confirmed that elevated PET signals corresponded to increased TREM2 expression, which was spatially localized to activated microglia in APP/PS1 mice brain sections. CONCLUSION: [68Ga]Ga-STZL730 is a novel peptide-based PET tracer that enables specific, noninvasive imaging of TREM2 expression in the CNS. It provides a promising tool for investigating neuroinflammation and TREM2-associated pathology in neurodegenerative diseases. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. Conflict of interest statement: Declarations. Ethics approval: All animal experimental procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals and were approved by the Ethics Committee of ShanghaiTech University (Approval Number: 20241224002). Consent to participate: Not applicable. Consent to publish: Not applicable. Competing Interests: The authors have no relevant financial or non-financial interests to disclose.”
Why does this matter? TREM2 is a hot target in Alzheimer’s and other CNS diseases, but visualizing its activity in real time has been a headache. This peptide tracer moves the field forward. It crosses the blood-brain barrier and delivers clear PET signals that map to TREM2 expression.
Key results:
[68Ga]Ga-STZL730 showed 99%+ radiochemical purity and robust in vitro stability.
The tracer’s binding affinity to TREM2 clocked in at a KD of 274 nM.
Brain uptake of the tracer was up over 100% in mice with LPS-induced neuroinflammation, and nearly 90% higher in Alzheimer’s model mice.
Knockout mice (no TREM2) had PET signals drop by more than 40%, proving specificity.
PET signals in Alzheimer’s mice matched up with microglial TREM2 expression, confirmed by autoradiography and immunostaining.
This is the kind of tool that lets researchers watch neuroinflammation unfold in real time. It’s a big leap for anyone studying TREM2’s role in Alzheimer’s, CNS injury, or even immunology. The peptide approach is fast, versatile, and clearly effective — new research directions just opened up.
For more on next-gen tracers and peptide innovation, check the peptide research index. This is the kind of peptide work that keeps neuroscience interesting.
Related Reading
The STRIDE Trial and Semaglutide: Implications for Clinical Vascular Practice.
News · J Med ChemStructure-Based Adaptation of a SARS-CoV-2 Neutralizing Peptide to New Virus Variants.
News · J Nucl MedCombining an α(v)β(6)-Targeted (177)Lu-Based Peptide Receptor Radionuclide Therapy with Olaparib to Boost Therapeutic Efficacy in Pancreatic Cancer.
For Research Use Only
All content published on Pushing Peptides is intended for educational and informational purposes only. The information provided is not intended as medical advice, diagnosis, or treatment. Peptides discussed in this article are research compounds and are not approved for human therapeutic use by the FDA or any other regulatory agency. All studies referenced involve animal models or in vitro research unless otherwise stated. Consult a qualified healthcare professional before making any decisions related to your health. Pushing Peptides does not sell peptides — we are a vendor directory and educational resource.