Prognostic value of [64Cu]GD2 PET beyond [18F]FDG PET in sarcoma patients

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Ziel/Aim: Despite their rarity, osteosarcoma, rhabdomyosarcoma, and Ewing’s sarcoma are causing approximately 10% of cancer-related deaths in children. GD2, a tumor-associated surface antigen, is variably expressed in sarcomas, yet its biological role and prognostic significance remain unclear. GD2-targeted antibody and CART-cell therapies have been developed and are under clinical investigation mainly in neuroblastoma patients. Here, we employed [ 64 Cu]GD2 whole body PET to non-invasively assess GD2 expression patterns in tumors and metastases, providing new insights into the role of GD2 in sarcomas. Methodik/Methods: We retrospectively analyzed 20 patients with histologically confirmed sarcoma who underwent [ 64 Cu]GD2 PET. Tumor uptake was quantified using SUVmean/SUVmax derived by a 50% threshold method. Patients were classified as GD2 positive (GD2+) if≥50% of their lesions showed an uptake equal to or greater than the blood pool. In 16 patients, additional [ 18 F]FDG PET scans were available for comparison. Tumor tissue samples were available in 13 patients and analyzed for GD2 expression by immunofluorescence (IF) staining as previously described [ 1 ]. Ergebnisse/Results: 8/20 patients were classified as GD2+according to [ 64 Cu]GD2 PET. Per definition GD2+patients showed significantly higher [ 64 Cu]GD2 uptake (7.7±3.6 vs 4.1±2.2) than GD2- patients. SUVmean correlated strongly and significantly with the IF GD2 expression score ex vivo ( r =0.7, p<0.01) . Off note, GD2- patients exhibited a significantly higher [ 18 F]FDG uptake in tumor lesions compared to GD2+patients (SUVmean: 6.2±3.6 vs 2.9±1.7). In line with these results, we observed a lower overall survival in GD2- patients compared to GD2+patients ( χ 2 =5.0, p=0.03; median OS GD2-: 5 months; GD2+: not reached). Schlussfolgerungen/Conclusion: [ 64 Cu]GD2 PET imaging revealed first evidence that the lack of GD2 expression is associated with increased metabolic activity and tumor aggressiveness in sarcomas. Beyond the role as therapeutic target, GD2 might have potential prognostic value and harbor a more complex role in tumor biology. Publication History Article published online: 02 April 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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