Initial Results of a Prospective Clinical Trial of ¹⁸F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers

Abstract

18 F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 Ffluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that 18 Ffluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of 18 F-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 5 19) or ILC (n 5 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of 18 F-fluciclovine. The SUV max , SUV mean , metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of 18 F-fluciclovine PET/CT were compared with those of 18 F-FDG PET/CT, when available, using the concordance correlation coefficient. Results: All locally advanced breast cancers were 18 F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, 18 F-fluciclovine-avid axillary nodes were seen in 20. 18 F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent 18 F-FDG PET/CT for comparison with 18 F-fluciclovine. Concordance for metabolic tumor volume between 18 F-fluciclovine and 18 F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUV max was weak (concordance correlation coefficient, 0.04; 95% confidence interval, −0.16-0.24). In patients with both modalities available (n 5 14), primary ILCs (n 5 4) demonstrated 18 F-fluciclovine avidity (median SUV max , 6.1; range, 4.5-10.9) greater than 18 F-FDG avidity (median SUV max , 3.7; range, 1.8-6.0). Primary IDCs (n 5 10) had a lower 18 F-fluciclovine avidity (median SUV max , 6.8; range, 3.6-9.9) than 18 F-FDG avidity (median SUV max , 10; range, 3.3-43.5). Conclusion: 18 F-fluciclovine PET/CT demonstrates potential for imaging of both IDC and ILC, including the detection of unsuspected extraaxillary nodal metastases. The low concordance for SUV max between 18 F-fluciclovine and 18 F-FDG suggests that these tracers measure different biologic phenomena within the tumor. The apparently higher uptake of 18 F-fluciclovine in ILC requires confirmation in a larger cohort.

Prospective Clinical Trial of 18F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers

“…Therefore, the development of better metabolic imaging agents for ILC could be clinically valuable. There is preliminary evidence that ILC may be more 18 F-fluciclovineavid than 18 F-FDG-avid (7,8). This study included 6 patients with ILC tumors, all of which were 18 F-fluciclovine-avid.…”

“…18 F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 F-fluciclovine), an amino acid analog labeled with the positron emitter 18 F, is under investigation as an imaging agent for several types of malignancy (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). 18 F-fluciclovine was recently approved by the U.S. Food and Drug Administration for the detection of recurrent prostate cancer.…”

“…18 F-fluciclovine was recently approved by the U.S. Food and Drug Administration for the detection of recurrent prostate cancer. Initial studies of 18 F-fluciclovine in breast cancer have provided encouraging results that warrant further investigation (7,8).…”

18F-Fluciclovine (FACBC) and Its Potential Use for Breast Cancer Imaging

“…Because amino acid transport is upregulated in many types of cancer, 18 F-fluciclovine has potential application in multiple types of cancer. In this issue of The Journal of Nuclear Medicine, 2 groups report promising preliminary results for FACBC in women with breast cancer naïve to therapy (2,3). These studies demonstrated substantially higher uptake of 18 F-fluciclovine in primary and metastatic breast cancers than in benign breast lesions and normal breast tissue.…”

Update on 18F-Fluciclovine PET for Prostate Cancer Imaging

“…Approval was granted to 18F-fluciclovine (trade name: Axumin) in May 2016 for the clinical indication of suspected prostate cancer recurrence based on elevated PSA levels following prior treatment and has Medicare pass through reimbursement effective January 2017. It should be noted that 18F-fluciclovine has been studied to image other malignancies such as breast (14) and glioma (15) but discussion of these applications is beyond the scope of this article.…”