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.

This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity (V(max)) and the muscle atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days, and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and V(max) increased from control of 6.4 to 6.6, 7.7, and 8.1 muscle lengths per second after 1, 2, and 3 days of CMV, respectively (P < 0.02). The increased V(max) compensated for the decreased tetanic force; consequently, compared with the controls, maximum power output was unchanged after 3 days of CMV. V(max) correlated with the volume density of abnormal myofibrils [y = 0.1x + 5.7 (r = 0.87, P < 0.01)]. In the diaphragm, MAF-box was overexpressed (355% of control) after 1 day of CMV, before the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in V(max) that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV.

CTA is a safe, non-invasive technique that precisely measures carotid artery area reduction and highly correlates to conventional arteriography. With this new technology, the current standards for carotid artery imaging may need to be reevaluated, and the precise role for helical CTA more clearly defined.

The time- and dose-dependent effects of acute high-dose corticosteroids on the diaphragm muscle are poorly defined. This study aimed to examine in rabbits the temporal relationships and dose-response effects of acute high-dose methylprednisolone succinate on diaphragmatic contractile and structural properties. Animals were assigned to groups receiving: (1) 80 mg/kg/day methylprednisolone (MP80) intramuscularly for 1, 2, and 3 days; (2) 10 mg/kg/day methylprednisolone (MP10, pulse-dose) for 3 days; or (3) saline (placebo) for 3 days; and (4) a control group. Diaphragmatic in vitro force-frequency and force-velocity relationships, myosin heavy chain (MyHC) isoform protein and mRNA, insulin-like growth factor-1 (IGF-1), muscle atrophy F-box (MAF-box) mRNA, and volume density of abnormal myofibrils were measured at each time-point. MP80 did not affect animal nutritional state or fiber cross-sectional area as assessed in separate pair-fed groups receiving methylprednisolone or saline for 3 days. Compared with control values, MP80 decreased diaphragmatic maximum tetanic tension (Po) by 19%, 24%, and 34% after 1, 2, and 3 days (P < 0.05), respectively, whereas MP10 decreased Po modestly (12%; P > 0.05). Vmax and MyHC protein proportions were unchanged in both the MP80 and MP10 groups. Maximum power output decreased after 2 and 3 days of MP80. Suppression of IGF-1 and overexpression of MAF-box mRNA occurred in both MP groups. Significant myofibrillar disarray was also observed in both MP groups. The decline in Po was significantly associated with the increased volume density of abnormal myofibrils. Thus, very high-dose methylprednisolone (MP80) can produce rapid reductions in diaphragmatic function, whereas pulse-dose methylprednisolone (MP10) produces only modest functional loss.

Computed tomographic arteriography (CTA) has emerged as a promising technique for less invasive imaging of the lower extremity arteries. The aim of this study was to determine the concordance between CTA and catheter arteriography (CA) in patients with peripheral arterial disease (PAD). Twenty-five patients underwent both CTA and CA, and each set of images was interpreted independently by 3 readers. The infrarenal arteries were divided into 16 segments, and each segment was scored as: 1 = stenosis <50%; 2 = 50-99% stenosis; 3 = occlusion. Modal scores from 3 readers were used to compare results for each segment, with CA assumed to represent true arterial anatomy. Agreement between CTA and CA readings was defined as: concordance (modal scores were identical); moderate discrepancy (MD) (modal scores differed by 1); or severe discrepancy (SD) (modal scores differed by 2). In total, 718 segments were assessed by both CTA and CA. For all segments, the sensitivity and specificity of CTA for <50% stenosis was 86% and 90%; for 50-99% stenosis, sensitivity and specificity were 79% and 89%; and for occlusion, 85% and 98%. Above-knee (AK) CTA scores had slightly better concordance of 86.1% than below-knee (BK) readings (82.3%) (p = 0.104). Severe discrepancies between AK CTA and CA scores were observed in 1.8% of segments compared to 5.4% of BK segments (p = 0.038). Poor CTA image quality was the cause in 20% of AK segments and 28% of BK segments. Poor CA image quality was the cause in 8% of AK and 7% of BK discrepancies. Registration disagreement (stenosis observed in a level in 1 study attributed to a different level in the other) accounted for 18% of AK and 17% of BK discrepancies. In 54% of AK and 48% of BK discrepancies, neither image quality nor registration errors were identified, indicating that inherent differences in the depiction of stenosis by CA and CTA were responsible. When discrepancies caused by registration error were excluded, SD observed in BK segments (4.0%) remained significantly higher than in AK segments (1.25%) (p = 0.029), and poor CTA quality image was the most common cause (76%) of severe BK discrepancies. In AK discrepancies without an identifiable technical cause, CTA uniformly showed more stenosis, suggesting greater CTA diagnostic precision in larger vessels. In general, agreement between CTA and CA was moderately good. Compared to CA, CTA may be better at depicting stenosis in large, proximal vessels owing to the superior accuracy of cross-sectional images in the measurement of stenosis. There appeared to be poorer CT resolution and higher frequency of severe discrepancies between CTA and CA in BK arteries.