Clinical comprehensive evaluation of [¹⁸F]AlF-FAP-NUR PET: multi-time-point imaging, head-to-head comparison with [¹⁸F]FDG.

Abstract

This study was designed to investigate the clinical feasibility of [¹⁸F]AlF-FAP-NUR, including the pharmacokinetics, radiation dosimetry estimation, and the head-to-head comparison with [¹⁸F]FDG. The head-to-head comparison study was designed to investigate the radiotracer uptake of [¹⁸F]AlF-FAP-NUR, to detect the primary and metastatic lesions in patients with various solid cancers, and to compare the results with those of [¹⁸F]FDG PET/CT. The correlation of FAP-expression (H-scores) and standardized uptake values (SUVs) derived from [¹⁸F]AlF-FAP-NUR were also included. Ten patients participated in a multi-time-point imaging protocol aimed at assessing pharmacokinetics and estimating radiation dosimetry. Radiation dosimetry calculations were performed using the OLINDA/EXM 2.0 software. For the comparative analysis between [¹⁸F]AlF-FAP-NUR and [¹⁸F]FDG PET, a cohort of 35 patients was included. SUVs and tumor-to-background ratios (TBRs) for primary and metastatic lesions were systematically collected and analyzed. To evaluate FAP expression in tissue samples, H-scores were obtained from FAP-immunohistochemistry (FAP-IHC) analyses of samples from 28 patients and correlated with the SUVs measured in [¹⁸F]AlF-FAP-NUR PET scans. Statistical analyses included non-parametric tests and correlation assessments, with a significance threshold set at P < 0.05. The study of multi-time-point imaging demonstrated that tumor SUV_max and TBRs increased over time, quickly peaking and remaining in a plateau phase [¹⁸F]AlF-FAP-NUR was mainly excreted from kidneys. The effective radiation dose of [¹⁸F]AlF-FAP-NUR was approximately 1.90E-02 mSv/MBq. In the head-to-head comparative study, [¹⁸F]AlF-FAP-NUR exhibited excellent detection capabilities for both primary and metastatic lesions, particularly in lymph node, bone, and lung metastases. The sensitivity and specificity of [¹⁸F]AlF-FAP-NUR PET/CT imaging for detecting lesions, as confirmed by pathology, were 86.7% and 98.3%, respectively. The positive predictive value (PPV) reached 89.7%, more than double that of [¹⁸F]FDG (PPV for FDG: 42.3%). Correlation analysis of the SUVs of [¹⁸F]AlF-FAP-NUR and FAP expression (based on H-score) showed that SUVs were all strongly correlated with FAP expression, with the SUV_max correlation value being as high as 0.7729 (P < 0.001). Our pilot study in patients with various solid tumors has demonstrated acceptable radiation dosimetry, favorable biodistribution, and significant [¹⁸F]AlF-FAP-NUR uptake in FAP-expressing tumors. The strong correlation with FAP expression further indicates the potential clinical usability of [¹⁸F]AlF-FAP-NUR PET.