Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

Purpose: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or F-FDG positron-emission-tomography (PET)-CT].

Methods: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with F-fluciclovine and Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of F-fluciclovine and Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test.

Results: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between Ga-PSMA-11 and standard-of care imaging. F-fluciclovine cDR was also significantly higher than Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with F-fluciclovine (n = 18) was significantly greater than for Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021].

Conclusion: In this exploratory trial, F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with F-fluciclovine than for Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study.

Clinical Trial Registration: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).