A Prospective Head-to-Head Comparison of HER2-Targeted and 18 F-FDG PET/CT for Detecting Axillary Lymph Node Metastases Among Newly Diagnosed HER2-Positive and HER2-Low Breast Cancer.

Abstract

To compare HER2-targeted with ¹⁸F-FDG PET/CT for detecting axillary lymph node metastasis in patients with newly diagnosed HER2-positive or HER2-low breast cancer. In this prospective study, HER2-expressed breast cancer participants underwent both 18 F-FDG and Al 18 F-NOTA-HER2-BCH PET/CT within 1 week. On the basis of IHC and/or FISH, participants were categorized as HER2-positive (n=25) or HER2-low (n=26). Histopathology or imaging follow-up served as reference standards. Statistical analyses utilized the paired McNemar test for diagnostic performance, and the Wilcoxon signed-rank and Mann-Whitney U tests for paired and unpaired comparisons of uptake parameters, respectively. Between August 2024 and October 2025, 51 participants with breast cancer were enrolled. Among 40 participants with lymph node metastasis, Al 18 F-NOTA-HER2-BCH detected metastatic lymph nodes exclusively in one HER2-positive participant and more lesions than 18 F-FDG in 11 cases. On a per-lesion analysis, Al 18 F-NOTA-HER2-BCH demonstrated significantly higher sensitivity, accuracy, and negative predictive value than 18 F-FDG for detecting metastatic axillary lymph nodes in the HER2-positive cohort (94%, 94%, 93% vs. 79%, 85%, 84%, all P <0.001). This superiority was particularly pronounced for small lymph nodes (<5 mm), with a detection rate of 90% versus 62% for 18 F-FDG ( P <0.001). Al 18 F-NOTA-HER2-BCH PET/CT directly influenced nodal staging and subsequent treatment decisions in 4 of 25 (16.0%) HER2-positive participants. In the HER2-low cohort, however, the diagnostic performance of the 2 tracers did not differ significantly, although 18 F-FDG PET/CT led to clinically relevant nodal upstaging in one case. Al 18 F-NOTA-HER2-BCH retains developmental potential for detecting axillary lymph node metastasis in HER2-positive breast cancer, complementing 18 F-FDG.