Amino Acid Metabolism as a Target for Breast Cancer Imaging

Abstract

Amino acids are an alternate energy source to glucose, and amino acid metabolism is up-regulated in multiple malignancies, including breast cancers. Multiple amino acid radiotracers have been used to image breast cancer with unique strengths and weaknesses. ¹¹C-methionine uptake correlates with S-phase fraction in breast cancer and may be useful for evaluation of treatment response. Invasive lobular breast cancers may demonstrate greater ¹⁸F-fluciclovine avidity than ¹⁸F-fluorodeoxyglucose. Thus, different histologic subtypes of breast cancer may use diverse metabolic pathways and may be better imaged by different tracers.

Keywords: Amino acid; Breast cancer; Fluciclovine; Methionine; PET/CT.

Figure 1

Greater ¹⁸F-fluciclovine avidity than ¹⁸F-FDG avidity in a patient with a right breast invasive lobular carcinoma (ILC). (A) Coronal CT, PET, and fused PET/CT images from a ¹⁸F-fluciclovine PET/CT demonstrate a ¹⁸F-fluciclovine-avid right breast ILC (arrow, SUV 7.1). (B) Coronal CT, PET, and fused PET/CT images from a ¹⁸F-FDG PET/CT on the same patient demonstrate lower FDG avidity (arrow, SUV 3.5). Adapted from Tade FI, Cohen MA, Styblo TM, et al. Anti-3-18F-FACBC (18F-Fluciclovine) PET/CT of Breast Cancer: An Exploratory Study. J Nucl Med. 2016 Sep;57(9):1357-63. doi: 10.2967/jnumed.115.171389. Epub 2016 Apr 7; with permission.

Figure 2

Reduction in ¹⁸F-fluciclovine avidity following neoadjuvant therapy in a 52-year-old woman with breast cancer. (A) Axial PET, CT, and fused images from a ¹⁸F-fluciclovine PET/CT at baseline demonstrate the ¹⁸F-fluciclovine-avid primary breast mass (arrow) and ¹⁸F-fluciclovine-avid axillary nodal metastases (dashed arrows). (B) Axial PET, CT, and fused PET/CT images from a ¹⁸F-fluciclovine PET/CT following neoadjuvant therapy demonstrate decreased ¹⁸F-fluciclovine avidity of all lesions to background. On pathology, there was a complete pathologic response, with no residual tumor. Adapted Ulaner GA, Goldman DA, Corben A, et al. Prospective clinical trial of 18F-fluciclovine PET/CT for determining the response to neoadjuvant therapy in invasive ductal and invasive lobular breast cancers. J Nucl Med. 2017;58(7):1037-1042; with permission.

Figure 3

Scatterplot demonstrating a strong correlation between ¹⁸F-fluciclovine SUV and percent tumor volume reduction on pathology in 24 patients with breast cancer following neoadjuvant therapy. Note that a 100% reduction in SUV on PET correlated with a 90-100% reduction in tumor reduction. Thus, while the correlation was strong, a 100% reduction in ¹⁸F-fluciclovine SUV could not distinguish a pathologic complete response from a pathologic non-complete response. ρ = Spearman’s rho. Adapted from Ulaner GA, Goldman DA, Corben A, et al. Prospective clinical trial of 18F-fluciclovine PET/CT for determining the response to neoadjuvant therapy in invasive ductal and invasive lobular breast cancers. J Nucl Med. 2017;58(7):1037-1042; with permission.