Immuno-PET/CT Imaging of Trop2 Expression with [18F]AlF-RESCA-RT4 Enhances Diagnosis of Breast Cancers and the Metastases.

This study aimed to evaluate human trophoblast cell surface antigen 2 (Trop2) expression across molecular subtypes of breast cancer and assess the diagnostic performance of a novel Trop2-targeted tracer, [18F]AlF-RESCA-RT4, compared with 18F-FDG PET/CT for patients with breast cancer.

Methods

This study analyzed Trop2 expression across 2 independent patient cohorts: a retrospective immunohistochemistry cohort and a prospective PET imaging cohort. In the retrospective cohort, Trop2 expression was detected using immunohistochemistry on tissue microarrays and quantified using the H-score (0-300). In the prospective imaging study, 35 patients with breast cancer underwent [18F]AlF-RESCA-RT4 immuno-PET/CT imaging to detect primary lesions and potential metastases. Pathology specimens were subsequently used for Trop2 immunohistochemistry staining to correlate with PET findings. Receiver-operating-characteristic curves were used to determine the tracer's diagnostic cutoff values. A subgroup analysis was performed for 14 patients who also underwent 18F-FDG PET/CT imaging.

Results

Retrospective immunohistochemistry results showed that Trop2 expression was significantly higher in breast tumor tissues than in adjacent normal tissues (P < 0.001), with no significant correlation with clinicopathologic features. In an ongoing clinical trial (NCT06715826), [18F]AlF-RESCA-RT4 uptake strongly correlated with Trop2 expression levels in the corresponding primary and metastatic tumor specimens (R 2 = 0.7346, P < 0.001). Cutoff values for the primary tumors (SUVmax, 2.66) and lymph node metastases (SUVmax, 1.74) showed high diagnostic sensitivity and specificity, with 97.1% and 93.1% (P < 0.001) for primary tumors and 88.2% and 97.2% (P < 0.001) for lymph node metastases, respectively. Compared with 18F-FDG, [18F]AlF-RESCA-RT4 demonstrated higher specificity (100% vs. 94.67%, P = 0.004) and accuracy (97.83% vs. 93.48%, P = 0.009) for lymph node metastases and detected more bone metastatic lesions (213 vs. 157). [18F]AlF-RESCA-RT4 immuno-PET/CT imaging demonstrated good diagnostic value for most invasive cancer types, except neuroendocrine tumors, and effectively differentiated tumors from inflammatory diseases.

Conclusion

Trop2 was highly expressed across all molecular subtypes of breast cancer and was not correlated with clinicopathologic features. [18F]AlF-RESCA-RT4 immuno-PET/CT is a highly sensitive and specific imaging tool for Trop2-positive breast cancer, offering superior diagnostic performance for nodal and bone metastases compared with 18F-FDG PET/CT.