Women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. Assessment of HER2 status in recurrent disease is usually made by core needle biopsy of a single lesion which may not be representative of the larger tumor mass or other sites of disease. Our long-range goal is to develop positron emission tomography (PET) of radiolabeled trastuzumab for systemically assessing tumor HER2 expression and identifying appropriate use of anti-HER2 therapies. The purpose of this study was to evaluate PET-CT of 64Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients with HER2-positive metastatic breast cancer. Methods Eight women with biopsy-confirmed HER2-positive metastatic breast cancer and no anti-HER2 therapy for ≥ 4 mo underwent complete staging, including 18F-fluorodeoxyglucose (FDG)/PET-CT. For 6 of the 8 patients, 64Cu-DOTA-trastuzumab injection (364-512 MBq, 5 mg trastuzumab) was preceded by trastuzumab infusion (45 mg). PET-CT (PET scan duration 1 h) was performed 21-25 (“Day 1”) and 47-49 (“Day 2”) h after 64Cu-DOTA-trastuzumab injection. Scan fields of view were chosen based on 18F-FDG/PET-CT. Lesions visualized relative to adjacent tissue on PET were considered PET-positive; analysis was limited to lesions identifiable on CT. Radiolabel uptake in prominent lesions was measured as maximum single-voxel standardized uptake value (SUVmax). Results Liver uptake of 64Cu was reduced approximately 75% with the 45 mg trastuzumab pre-dose, without significant effect on tumor uptake. The study included 89 CT-positive lesions; detection sensitivity was 77, 89 and 93% for Day 1, Day 2 and 18F-FDG, respectively. On average, tumor uptake was similar for 64Cu-DOTA-trastuzumab and 18F-FDG [SUVmax (mean, range): Day 1 (8.1, 3.0-22.5, n=48); Day 2 (8.9, 0.9-28.9, n=38); 18F-FDG (9.7, 3.3-25.4, n=56)], but the extent of same-lesion uptake was not correlated between the 2 radiotracers. No toxicities were observed, and estimated radiation dose from 64Cu-DOTA-trastuzumab was similar to 18F-FDG. Conclusion 64Cu-DOTA-trastuzumab visualizes HER2-positive metastatic breast cancer with high sensitivity, and is effective in surveying disseminated disease. A 45 mg trastuzumab pre-dose provides a 64Cu-DOTA-trastuzumab biodistribution favorable for tumor imaging. 64Cu-DOTA-trastuzumab/PET-CT warrants further evaluation for assessing tumor HER2 expression and measuring delivery of trastuzumab-based therapy.

Adipose tissue stores energy and is the largest endocrine organ in the body, producing several adipokines. However, among these adipokines, few play a role in the positive metabolism that promotes good health. Secreted frizzled-related protein (Sfrp)-5, an antagonist that directly binds to Wnt, has attracted interest due to its favorable effects on atherosclerotic cardiovascular disease (ASCVD). This review focuses on Sfrp5 biology and the roles of the Sfrp5/Wnt system in ASCVD.

Music and speech are two sounds that are unique to human beings and encountered in daily life. Both are transformed by the auditory pathway from an initial acoustical encoding to higher level cognition. Most studies of speech and music processing are focused on the cortex, and the subcortical response to natural, polyphonic music is essentially unstudied. The goal of this study was to compare the subcortical encoding of music and speech using the auditory brainstem response (ABR). While several methods have recently been developed to derive the ABR to continuous speech, they are either not applicable to music or give poor results. In this study, we explored deriving the ABR through deconvolution using three regressors: 1) the half-wave rectified stimulus waveform, 2) the modeled inner hair cell potential, and 3) the auditory nerve model firing rate (ANM), where the latter two were generated from a computational auditory periphery model. After quantitatively comparing the three regressors, we found the ANM regressor yields robust and interpretable ABR waveforms to diverse genres of music and multiple types of speech stimuli. We then used the ANM-derived ABRs to compare the subcortical responses to music and speech and found that they are highly similar in morphology. We further investigated cortical responses using the same deconvolution method, and found the responses there were also quite similar, which was unexpected based on previous studies. Our study first developed approach that can be used to investigate subcortical encoding and processing for both natural speech and music with the potential for use in cortical encoding. Based on that, we concluded that when accounting for acoustical differences' nonlinear effects on peripheral encoding, the derived music and speech brainstem responses are highly correlated.

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