Al18F-NOTA-HER2-BCH versus 18F-FDG PET/CT in evaluating newly diagnosed HER2-low breast cancer patients.

PURPOSE: To assess the diagnostic performance and the whole-body heterogeneity of HER2 expression on Al18F-NOTA-HER2-BCH PET/CT in patients with HER2-low breast cancer.

METHODS

In this prospective study conducted from November 2021 to March 2024, participants with HER2-low breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. Participants were pathologically confirmed as HER2-low (immunohistochemistry score of 1 + or 2 + without HER2 gene amplification on in situ hybridization). PET/CT images were acquired 3.5 h after injection of 200 MBq of Al18F-NOTA-HER2-BCH. The maximum standardized uptake value (SUVmax) and target-to-background ratios (TBR) were used to quantify tracer uptake.

RESULTS

Fifty-two participants with HER2-low breast cancer (mean age, 53.0 ± 11.0; 52 females) underwent Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT with paired tumor biopsies. No adverse events occurred. The median SUVmax and TBR of 52 HER2-low biopsy lesions on Al18F-NOTA-HER2-BCH PET/CT were lower than that on 18F-FDG PET/CT (6.6 vs. 10.5, P <.001; 8.0 vs. 10.6, P =.009). A total of 269 suspicious lesions were detected, 18F-FDG PET/CT depicted more suspected HER2-low positive lesions in breast (100% vs. 100%), chest wall (100% vs. 100%), lymph node (83.9% vs. 77.7%), bone (100% vs. 93.2%), liver (66.7% vs. 52.4%) and lung (86.7% vs. 75.0%) than Al18F-NOTA-HER2-BCH PET/CT. Additionally, clear interindividual and intraindividual differences on Al18F-NOTA-HER2-BCH tracer uptake was noted between participants, between different metastases in the same participants, even within different organ systems.

CONCLUSION

The visualization of HER2-low breast cancer with Al18F-NOTA-HER2-BCH PET/CT was feasible and safe. The observed intra- and inter-individual heterogeneity in the uptake of Al18F-NOTA-HER2-BCH indicates its potential use as a noninvasive tool for assessing disease heterogeneity and identifying patients who may derive clinical benefit from HER2-targeted therapies.