Clinical Evaluation of [¹⁸F]AlF-NOTA-GL01 PET/CT in patients with solid tumors: a prospective comparison with [¹⁸F]FDG and an exploratory [¹⁸F]FAPI-42 subset.

Abstract

This prospective study evaluated the clinical performance of [¹⁸F]AlF-NOTA-GL01 PET/CT, examined the relationship between tracer uptake and tumor FAP expression, and performed head-to-head comparisons with [¹⁸F]FDG and [¹⁸F]FAPI-42 PET/CT in exploratory subset. Between August 2025 and March 2026, 106 patients completed [¹⁸F]AlF-NOTA-GL01 PET/CT and paired-tracer PET/CT; 103 underwent paired [¹⁸F]FDG PET/CT and 3 underwent paired [¹⁸F]FAPI-42 PET/CT. Lesion SUVmax and tumor-to-background ratio (TBR) were compared on a lesion basis. In tumors with available histology, FAP expression was quantified by immunohistochemistry and correlated with lesion SUVmax. Patient- and lesion-based diagnostic performance was assessed against a composite reference standard. The final cohort comprised 106 patients (55 men, 51 women; mean age, 61.3 ± 9.0 years), including 102 malignant tumors and 4 benign lesions. Lesion [¹⁸F]AlF-NOTA-GL01 SUVmax correlated strongly with tumor FAP expression (r = 0.754, P < 0.001) and increased across low, intermediate, and high FAP-expression tumors. In patient-based analysis, [¹⁸F]AlF-NOTA-GL01 showed higher sensitivity than [¹⁸F]FDG (98.9% vs. 90.8%, P = 0.039), with comparable specificity (62.5% vs. 62.5%, P = 1.000). In lesion-based analysis, [¹⁸F]AlF-NOTA-GL01 outperformed [¹⁸F]FDG in sensitivity (96.4% vs. 71.3%, P < 0.001), specificity (50.6% vs. 24.7%, P = 0.003), and accuracy (90.5% vs. 65.3%, P < 0.001). In an exploratory subset, [¹⁸F]AlF-NOTA-GL01 showed lower normal-organ background and higher lesion-to-background ratios than [¹⁸F]FAPI-42. [¹⁸F]AlF-NOTA-GL01 uptake was associated with tumor FAP expression and demonstrated higher lesion-based sensitivity and accuracy than [¹⁸F]FDG in this single-center cohort, although specificity remained modest. These findings support further clinical development of [¹⁸F]AlF-NOTA-GL01 as a broadly applicable, scalable FAP-targeted PET agent.