title: 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)F-fluciclovine) 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)F-fluciclovine 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 = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, 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 SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity (median SUVmax, 6.1; range, 4.5-10.9) greater than (18)F-FDG avidity (median SUVmax, 3.7; range, 1.8-6.0). Primary IDCs (n = 10) had a lower (18)F-fluciclovine avidity (median SUVmax, 6.8; range, 3.6-9.9) than (18)F-FDG avidity (median SUVmax, 10; range, 3.3-43.5).
  
  
  CONCLUSIONS
  (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 SUVmax 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.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Departments of Radiology and Pharmacology, Weill Cornell Medical College, New York, New York ulanerg@mskcc.org.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ulaner
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Goldman
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Hanh
authors.initials: H
authors.lastname: Pham
authors.affiliation: Hunter College of the City College of New York, New York, New York.
authors.forename: Raychel
authors.initials: R
authors.lastname: Castillo
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Radiochemistry & Molecular Imaging Probe Core, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Serge K
authors.initials: SK
authors.lastname: Lyashchenko
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Departments of Radiology and Pharmacology, Weill Cornell Medical College, New York, New York Radiochemistry & Molecular Imaging Probe Core, Memorial Sloan Kettering Cancer Center, New York, New York Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Chau
authors.initials: C
authors.lastname: Dang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002264:Carboxylic Acids; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000000981:diagnostic imaging* / Q000473:pathology; D003503:Cyclobutanes; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010865:Pilot Projects; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002264:Carboxylic Acids; D003503:Cyclobutanes; D019275:Radiopharmaceuticals; C117460:fluciclovine F-18
keywords: 18F-FACBC; 18F-fluciclovine; PET/CT; breast cancer; ductal; lobular