Anti-3-[18F] FACBC (Fluciclovine) PET-CT of Breast Cancer An Exploratory Study

The purpose of this study is to explore the uptake of the synthetic amino acid analog positron emission tomography (PET) radiotracer anti-3-[¹⁸F] FACBC (fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. Methods: Twelve women with breast lesions underwent 45 minute dynamic PET-CT of the thorax after intravenous administration of 366.3 ±14.8 (337.44 - 394.05) MBq of fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in maximum standard uptake value (SUV_max) and tumor to background ratios between malignant and benign tissue were calculated. Correlation of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham Grade (NG). Results: There were 17 breast lesions (4 benign, 13 malignant) including 7/13 invasive ductal, 5/13 invasive lobular, and 1/13 metaplastic carcinomas. There was a significant difference in mean SUV_max ± standard deviation (SD) of malignant (6.15±3.2, 6.01±3.15, 5.68±2.82, and 5.59±2.95) vs benign (1.26±0.57, 1.21±0.53, 1.22±0.57 and 1.11±0.54) lesions at 5, 17, 29 and 41mins respectively (all p≤0.0001). Tumor to background (aorta, normal breast and marrow) ratios were also significantly higher in malignant compared to benign breast lesions (all P≤0.02). Highest fluciclovine activity seems to be present in triple negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUV_max [R1=0.48(P = 0.03), R2=0.44(P = 0.03), R3= 0.46(P = 0.03), R4 =0.43(0.06)]. In 7 patients, fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. Conclusion: The uptake characteristics of fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspect breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies utilizing fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread

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