image: Figure 1. PD-L1 targeting molecular imaging in head and neck carcinoma: A head-to-head comparison of [18F]AlF-NOTA-PCP2 PET and [18F]FDG PET/CT.
Credit: Images created by Yong Wang et al., Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
NEW ORLEANS—A first-in-class peptide-based PET tracer, 18F-AlF-NOTA-PCP2, can effectively measure PD-L1 expression in patients with head and neck cancers, outperforming the conventional tracer 18F-FDG. 18F-AlF-NOTA-PCP2 uptake strongly correlated with PD-L1 levels, highlighting the tracer’s potential to improve patient stratification and guide personalized treatment strategies. This research was presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2025 Annual Meeting, and the grouping of images comparing 18F-AlF-NOTA-PCP2 and 18F-FDG uptake has been selected as the 2025 SNMMI Henry N. Wagner, Jr., Image of the Year.
Each year, SNMMI chooses an image that best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging. The state-of-the-art technologies captured in these images demonstrate the capacity to improve patient care by detecting disease, aiding diagnosis, improving clinical confidence, and providing a means of selecting appropriate treatments. This year, the SNMMI Image of the Year was chosen from more than 1,300 abstracts submitted for the meeting.
PD-L1 expression is relatively common in head and neck cancers, particularly in head and neck squamous cell carcinoma (HNSCC)—the most prevalent subtype. Previous studies have primarily correlated FDG PET uptake and PD-L1 expression as determined by immunohistochemistry. However, because immunohistochemistry is typically performed on small, localized biopsy samples, it may not capture the full heterogeneity of PD-L1 expression—limiting the accuracy of such correlations.
“To address this limitation, we developed 18F-AlF-NOTA-PCP2, a novel PD-L1-targeted peptide-based tracer designed to enhance hydrophilicity and achieve superior tumor-to-background ratios. Compared with 68Ga analogs, the 18F-AlF tracer can be produced with a high-yield dosage and is convenient for the following clinical translation applications,” said Man Hu, MD, professor at Shandong Cancer Hospital and Institute in Jinan, Shandong, China. “This study evaluates 18F-AlF-NOTA-PCP2 in head and neck carcinoma patients, focusing on safety, biodistribution, specificity, and imaging performance.”
To assess the PD-L1 binding specificity of 18F-AlF-NOTA-PCP2, researchers first conducted in vitro competitive inhibition studies and preclinical imaging in mice with head and neck cancer xenografts. In a clinical study, 24 patients with HNSCC underwent 18F-AlF-NOTA-PCP2 PET/CT imaging, with 16 also receiving paired 18F-FDG PET scans for comparison. Researchers analyzed tracer uptake, safety, biodistribution, and the correlation between imaging results and PD-L1 expression confirmed by immunohistochemistry.
Preclinical studies showed that 18F-AlF-NOTA-PCP2 binds PD-L1 with high affinity and specifically targets PD-L1-positive tumors. In the patient study, tracer uptake strongly correlated with PD-L1 expression measured by immunohistochemistry, confirming its ability to noninvasively detect PD-L1 in vivo. A direct comparison of 18F-AlF-NOTA-PCP2 and 18F-FDG PET revealed only a moderate correlation, highlighting the limited ability of 18F-FDG to predict PD-L1 expression.
“Our study demonstrates the feasibility of 18F-AlF-NOTA-PCP2 for real-time PD-L1 imaging in HNSCC, paving the way for optimized treatment strategies,” noted Yong Wang, MD, associate professor at Shandong Cancer Hospital and Institute. “Combining FDG PET with immuno-PET tracers like 18F-AlF-NOTA-PCP2 could offer a more comprehensive understanding of tumor biology, improving patient selection and informing tailored immunotherapy strategies.”
According to Heather Jacene, MD, SNMMI Scientific Program Committee chair, the introduction of a targeted, specific tracer for PD-L1 expression could be transformative for molecular imaging and nuclear medicine. “This advancement has the potential to significantly enhance the precision of imaging in oncology, enabling clinicians to more accurately track immune-related biomarkers and make real-time adjustments to treatment strategies,” she said.
Pending further studies and regulatory approval, 18F-AlF-NOTA-PCP2 could become available for clinical use in the next two to three years. As the technology advances, it has the potential to be integrated into standard care for patients undergoing immunotherapy, providing an improved method to assess and monitor PD-L1 expression in the context of immunotherapy.
Abstract 251095. “Can [18F]FDG-PET/CT Predict PD-L1 Expression in Head and Neck Carcinoma? A Head-to-Head Comparison with a Novel PD-L1 PET Tracer.” Yong Wang, Zhiguo Liu, Jinming Yu, and Man Hu, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Link to Abstract
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All 2025 SNMMI Annual Meeting abstracts can be found online.
About the Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.
SNMMI’s members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snmmi.org.
Journal
Journal of Nuclear Medicine
Article Title
Can [18F]FDG-PET/CT Predict PD-L1 Expression in Head and Neck Carcinoma? A Head-to-Head Comparison with a Novel PD-L1 PET Tracer