Abstract
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Objectives Fluorine-18-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (18F-Fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins are upregulated in breast malignancies, so we hypothesized that 18F-Fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of 18F-Fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC).
Methods Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq (10 mCi) +/- 10% of 18F-Fluciclovine. The SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion avidity (TLA) were obtained for the primary breast tumor, axillary lymph nodes, and extra-axillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of 18F-Fluciclovine PET/CT were compared with those of 18F-FDG PET/CT, when available, using the concordance correlation coefficient.
Results All locally advanced breast cancers were 18F-Fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, 18F-Fluciclovine-avid axillary nodes were seen in 20. 18F-Fluciclovine detected pathologically proven extra-axillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients had 18F-FDG PET/CT for comparison with 18F-Fluciclovine. Concordance for MTV between 18F-Fluciclovine and 18F-FDG was strong (CCC: 0.89, 95% CI: 0.73-0.96), but concordance for SUVmax was weak (CCC: 0.04, 95% CI: -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated 18F-Fluciclovine avidity (median SUVmax: 6.1, range: 4.5-10.9) greater than 18F-FDG avidity (median SUVmax: 3.7, range: 1.8-6.0). Primary IDCs (n = 10) had a lower 18F-Fluciclovine avidity (median SUVmax: 6.8, range: 3.6-9.9) than 18F-FDG avidity (median SUVmax 10, range: 3.3-43.5).
Conclusions 18F-Fluciclovine PET/CT demonstrates potential for imaging of both IDC and ILC, including the detection of unsuspected extra-axillary nodal metastases. The low concordance for SUVmax between 18F-Fluciclovine and 18F-FDG suggests that these tracers measure different biologic phenomena within the tumor. The apparently higher uptake of 18F fluciclovine in ILC requires confirmation in a larger cohort. This study is supported by Susan G. Komen for the Cure Research Grant KG110441, MSKCC Biostatistics Core and Radiochemistry & Molecular Imaging Probe Cores (P30 CA008748), and the MSKCC Breast Cancer Research Fund.