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

Abstract

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. <b>Methods:</b> 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. <b>Results:</b> Retrospective immunohistochemistry results showed that Trop2 expression was significantly higher in breast tumor tissues than in adjacent normal tissues (<i>P</i> < 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 (<i>R</i> ² = 0.7346, <i>P</i> < 0.001). Cutoff values for the primary tumors (SUV_max, 2.66) and lymph node metastases (SUV_max, 1.74) showed high diagnostic sensitivity and specificity, with 97.1% and 93.1% (<i>P</i> < 0.001) for primary tumors and 88.2% and 97.2% (<i>P</i> < 0.001) for lymph node metastases, respectively. Compared with ¹⁸F-FDG, [¹⁸F]AlF-RESCA-RT4 demonstrated higher specificity (100% vs. 94.67%, <i>P</i> = 0.004) and accuracy (97.83% vs. 93.48%, <i>P</i> = 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. <b>Conclusion:</b> 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.