Alfatide[18F]

For the further study of [19F]‐alfatide, the development of highly sensitive analytical methods for its determination is an urgent issue. In this paper, a method for simultaneously determining [19F]‐alfatide and alfatide using liquid chromatography/tandem mass spectrometry was created and validated. The plasma samples were pretreated using the protein precipitation method. Poroshell 120 EC‐C18 (4.6 × 50 mm, 2.7 μm, Agilent) was used for the separation of the analytes to be measured. The mobile phase, consisting of acetonitrile and water (0.1% acetic acid, 50:50, v/v), was delivered at a flow rate of 0.60 ml/min for sample analysis. Positive electrospray ionization was performed using multiple‐reaction monitoring with transitions of m/z 715.2 → 636.6 for [19F]‐alfatide, the ion pairs 700.3 → 851.5 for alfatide and the ion pairs 237.1 → 194.2 for carbamazepine (internal standard). According to the results, the method had high specificity, precision and accuracy as well as an extended linear range. The matrix effect and extraction recovery were also acceptable. The method was successfully applied to the pharmacokinetic study of [19F]‐alfatide in rats.

¹⁸F-Alfatide II has been translated into clinical use and been proven to have good performance in identifying breast cancer. In this study, we investigated ¹⁸F-Alfatide II for evaluation of axillary lymph nodes (ALN) in breast cancer patients and compared the performance with ¹⁸F-FDG.

A total of 44 female patients with clinically suspected breast cancer were enrolled and underwent ¹⁸F-Alfatide II and ¹⁸F-FDG PET/CT within a week. Tracer uptakes in ALN were evaluated by visual analysis, semi-quantitative analysis with maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), and SUV_max ratio of target/non-target (T/NT).

Among 44 patients, 37 patients were pathologically diagnosed with breast cancer with metastatic (17 cases) or non-metastatic (20 cases) ALN. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of visual analysis were 70.6%, 90%, 81.1%, 85.7%, and 78.3% for ¹⁸F-Alfatide II, 64.7%, 90%, 78.4%, 84.6%, and 75% for ¹⁸F-FDG, respectively. By combining ¹⁸F-Alfatide II and ¹⁸F-FDG, the sensitivity significantly increased to 82.4%, the specificity was 85%, the accuracy increased to 83.8%, the PPV was 82.4%, and the NPV significantly increased to 85.0%. Three cases of luminal B subtype were false negative for both ¹⁸F-Alfatide II and ¹⁸F-FDG. The other 2 false negative cases of ¹⁸F-Alfatide II were triple-negative subtype and 3 false negative cases of ¹⁸F-FDG were luminal B subtype too. The AUCs of three semi-quantitative parameters (SUV_max, SUV_mean, T/NT) for ¹⁸F-Alfatide II were between 0.8 and 0.9, whereas those for ¹⁸F-FDG were more than 0.9. ¹⁸F-Alfatide II T/NT had the highest Youden index (76.5%), specificity (100%), accuracy (89.2%), and PPV (100%) among these semi-quantitative parameters. ¹⁸F-Alfatide II uptake as well as ¹⁸F-FDG uptake in metastatic axillary lymph nodes (MALN) was significantly higher than that in benign axillary lymph nodes (BALN). Both ¹⁸F-Alfatide II and ¹⁸F-FDG did not show difference in primary tumor uptake irrespective of ALN status.

¹⁸F-Alfatide II can be used in breast cancer patients to detect metastatic ALN, however, like ¹⁸F-FDG, with high specificity but relatively low sensitivity. The combination of ¹⁸F-Alfatide II and ¹⁸F-FDG can significantly improve sensitivity and NPV. ¹⁸F-Alfatide II T/NT may serve as the most important semi-quantitative parameter to evaluate ALN.