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

(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). 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. 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). (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.

Ulaner GA ，Goldman DA ，Gönen M ，Pham H ，Castillo R ，Lyashchenko SK ，Lewis JS ，Dang C ... -  《-》

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

18F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells. 18F-fluciclovine PET/CT visualizes malignancy, including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in 18F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in 18F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated. Methods: Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer (n = 18) or invasive lobular breast cancer (n = 6) underwent 18F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background 18F-fluciclovine avidity. The relationship between changes in 18F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation. Results: The median decrease in the corrected SUVmax of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in 18F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90; P < 0.001). Conclusion: Changes in 18F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study.

Ulaner GA ，Goldman DA ，Corben A ，Lyashchenko SK ，Gönen M ，Lewis JS ，Dickler M ... -  《-》

Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma.

Although guidelines such as those of the National Comprehensive Cancer Network consider (18)F-FDG PET/CT for systemic staging of newly diagnosed stage III breast cancer patients, factors in addition to stage may influence the utility of PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than invasive ductal carcinoma (IDC) on (18)F-FDG PET, we hypothesized that tumor histology may be one such factor. We evaluated PET/CT systemic staging of patients newly diagnosed with ILC compared with IDC. In this Institutional Review Board-approved retrospective study, our Hospital Information System was screened for ILC patients who underwent PET/CT in 2006-2013 before systemic or radiation therapy. Initial stage was determined from examination, mammography, ultrasound, MR, or surgery. PET/CT was performed to identify unsuspected distant metastases. A sequential cohort of stage III IDC patients was evaluated for comparison. Upstaging rates were compared using the Pearson χ(2) test. The study criteria were fulfilled by 146 ILC patients. PET/CT revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I, 2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged only by the CT component of the PET/CT, as the metastases were not (18)F-FDG-avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were upstaged to IV by PET/CT. All 20 demonstrated (18)F-FDG-avid metastases. The relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC patients was 1.98 times (95% confidence interval, 0.98-3.98) that of stage III ILC patients (P = 0.049). For (18)F-FDG-avid metastases, the relative risk of PET/CT revealing unsuspected (18)F-FDG-avid distant metastases in stage III IDC patients was 2.82 times (95% confidence interval, 1.26-6.34) that of stage III ILC patients (P = 0.007). (18)F-FDG PET/CT was more likely to reveal unsuspected distant metastases in stage III IDC patients than in stage III ILC patients. In addition, some ILC patients were upstaged by non-(18)F-FDG-avid lesions visible only on the CT images. Overall, the impact of PET/CT on systemic staging may be lower for ILC patients than for IDC patients.

Hogan MP ，Goldman DA ，Dashevsky B ，Riedl CC ，Gönen M ，Osborne JR ，Jochelson M ，Hudis C ，Morrow M ，Ulaner GA ... -  《-》

Anti-3-18F-FACBC (18F-Fluciclovine) PET/CT of Breast Cancer: An Exploratory Study.

The purpose of this study was to explore the uptake of the synthetic amino acid analog PET radiotracer anti-3-(18)F-FACBC ((18)F-fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. Twelve women with breast lesions underwent 45-min dynamic PET/CT of the thorax after intravenous administration of 366.3 ± 14.8 (337.44-394.05) MBq of (18)F-fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, and 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in SUVmax and tumor-to-background ratios between malignant and benign tissue were calculated. Correlations of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham grade (NG). There were 17 breast lesions (4 benign, 13 malignant) including 7 of 13 invasive ductal, 5 of 13 invasive lobular, and 1 of 13 metaplastic carcinomas. There was a significant difference in mean SUVmax ± SD of malignant (6.2 ± 3.2, 6.0 ± 3.2, 5.7 ± 2.8, and 5.6 ± 3.0) versus benign (1.3 ± 0.6, 1.2 ± 0.5, 1.2 ± 0.6, and 1.1 ± 0.5) lesions at 5, 17, 29, and 41 min, respectively (all P ≤ 0.0001). Tumor-to-background (aorta, normal breast, and marrow) ratios were also significantly higher in malignant than benign breast lesions (all P ≤ 0.02). The highest (18)F-fluciclovine activity seems to be present in triple-negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUVmax (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, (18)F-fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. The uptake characteristics of (18)F-fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspected breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies using (18)F-fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread.

Tade FI ，Cohen MA ，Styblo TM ，Odewole OA ，Holbrook AI ，Newell MS ，Savir-Baruch B ，Li X ，Goodman MM ，Nye JA ，Schuster DM ... -  《-》

More advantages in detecting bone and soft tissue metastases from prostate cancer using (18)F-PSMA PET/CT.

Pianou NK ，Stavrou PZ ，Vlontzou E ，Rondogianni P ，Exarhos DN ，Datseris IE ... -  《Hellenic Journal of Nuclear Medicine》