CXCR4-targeted PET/CT with [¹⁸F]AlF-NOTA-QHY-04 in primary central nervous system lymphoma: a prospective comparison with MRI and [¹⁸F]FDG PET/CT.

This study aimed to evaluate the diagnostic performance of [¹⁸F]AlF-NOTA-QHY-04 PET/CT, a novel CXCR4-targeted imaging agent, in detecting primary central nervous system lymphoma (PCNSL) at initial diagnosis and suspected recurrence, in comparison with contrast-enhanced magnetic resonance imaging (CE-MRI) and [¹⁸F]FDG PET/CT.

We prospectively enrolled patients with suspected PCNSL between September 2022 and December 2024. A total of 29 patients underwent both CE-MRI and [¹⁸F]AlF-NOTA-QHY-04 PET/CT, with 20 patients also receiving [¹⁸F]FDG PET/CT. Biopsy pathology served as the reference standard for newly diagnosed lesions. Recurrence was assessed using a composite reference standard based on CE-MRI, clinical follow-up, and cerebrospinal fluid (CSF) findings when available; an exploratory sensitivity analysis excluded MRI-dependent cases. Imaging parameters including the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratios (TBR) were calculated. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis and compared.

Six treatment-naïve patients (14 lesions) and 16 patients with recurrence (16 lesions) were confirmed, along with 7 patients without recurrence. Both primary and recurrent lesions showed intense tracer uptake on [¹⁸F]AlF-NOTA-QHY-04 PET/CT, characterized by notably high TBR. In the 20-patient subgroup undergoing both PET scans, [¹⁸F]AlF-NOTA-QHY-04 demonstrated significantly lower absolute SUVmax compared to [¹⁸F]FDG (median: 2.42 vs. 11.73, P < 0.001) but a substantially higher TBR-SUVmax (median: 42.75 vs. 1.07, P < 0.001), leading to the identification of more positive lesions (14 vs. 7, P = 0.023). Relative to the composite reference standard, [¹⁸F]AlF-NOTA-QHY-04 PET/CT achieved sensitivity and accuracy (87.50% and 90.91%, respectively) comparable to CE-MRI (100% for both, P > 0.05) and significantly superior to [¹⁸F]FDG PET/CT (43.75% and 59.09%, P = 0.023). ROC analysis identified [¹⁸F]AlF-NOTA-QHY-04 SUVmax as the optimal diagnostic parameter (AUC = 0.979).

[¹⁸F]AlF-NOTA-QHY-04 PET/CT demonstrated high tumor-to-background contrast in PCNSL, consistent with its low background brain uptake. It shows diagnostic accuracy comparable to CE-MRI and significantly superior to [¹⁸F]FDG PET/CT, demonstrating high potential as a valuable imaging tool for the diagnosis and restaging of PCNSL.
Non-Communicable Diseases
Care/Management

Authors

Pang Pang, Xing Xing, Liu Liu, Zhao Zhao, Li Li, Xu Xu, Pei Pei, Yu Yu, Chen Chen, Liu Liu
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