Association of Epicardial Adipose Tissue With Left Ventricular Strain and MR Myocardial Perfusion in Patients With Known Coronary Artery Disease.

BACKGROUND: Epicardial adipose tissue (EAT) may have a paracrine effect on coronary microcirculation and myocardium. However, it is unclear whether EAT is linked to cardiac function and perfusion. PURPOSE: To investigate the association of EAT with left ventricular (LV) strain and myocardial perfusion in patients with coronary artery disease (CAD). STUDY TYPE: Retrospective. POPULATION: A total of 78 patients with CAD and 20 healthy controls. The patients were further divided into high (n = 39) and low EAT volume (n = 39) groups according to median EAT volume. FIELD STRENGTH/SEQUENCE: A 1.5 T, balanced steady-state free precession, inversion recovery prepared echo-planar, and segmented-turbo fast low-angle shot (FLASH) phase-sensitive inversion recovery (PSIR) sequences. ASSESSMENT: EAT volume was measured by manually tracing the epicardial border and the visceral layer of pericardium on the short-axis cine stacks. LV strain parameters included global radial (GRS), circumferential (GCS), and longitudinal peak strain (GLS). Perfusion indices included upslope, perfusion index, time-to-maximum signal intensity (TTM), and maximum signal intensity (MaxSI). STATISTICAL TESTS: One-way analysis of variance or Kruskal-Wallis rank tests, Chi-squared or Fisher exact tests. Multivariate linear regression analyses. A P value < 0.05 was considered statistically significant. RESULTS: The parameters of GRS GCS, GLS, upslope, perfusion index, and MaxSI were significantly lower in the patients when compared to the controls. Moreover, the high EAT volume group presented significantly longer TTM values and lower GRS, GCS, GLS, upslope, perfusion index, and MaxSI than the low EAT volume group. Multivariate linear regression analyses demonstrated that EAT was independently associated with GRS, GCS, GLS, upslope, perfusion index, TTM, and MaxSI in patients. EAT and upslope were independently associated with GRS, while EAT and perfusion index were both independently associated with GCS and GLS. DATA CONCLUSION: EAT was associated with parameters of LV function and perfusion, and myocardial perfusion was independently associated with LV strain in patients with CAD. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Evaluation of A Novel GLP-1R Ligand for PET Imaging of Prostate Cancer.

BACKGROUND: Glucagon-like peptide 1 receptor (GLP-1R) is an important biomarker for diagnosis and therapy of the endocrine cancers due to overexpression. Recently, in human prostate cancer cell lines the receptor was also observed, therefore it may be a potential target for the disease. 18F-Al-NOTA-MAL-Cys39- exendin-4 holds great promise for GLP-1R. Therefore, the feasibility of the 18F-labeled exendin-4 analog for prostate cancer imaging was investigated. METHODS: New probe 18F-Al-NOTA-MAL-Cys39-exendin-4 was made through one-step fluorination. Prostate cancer PC3 cell xenograft model mice were established to primarily evaluate the imaging properties of the tracer via small animal PET studies in vivo. Pathological studies and Western Blots were also performed. RESULTS: PC-3 prostate xenografts were clearly imaged under baseline conditions. At 30 and 60 min postinjection, the tumor uptakes were 2.90±0.41%ID/g and 2.26±0.32 %ID/g respectively. The presence of cys39-exendin-4 significantly reduced the tumor uptake to 0.82±0.10 %ID/g at 60 min p.i. Findings of ex vivo biodistribution studies were similar to those of in vivo PET imaging. The tumors to blood and muscles were significantly improved with the increase of time due to rapid clearance of the tracer from normal organs. Low levels of radioactivity were also detected in the GLP-1R positive tumor and normal organs after coinjection with excessive unlabeled peptides. Immunohistochemistry and Western Blots results confirmed that GLP-1R was widely expressed in PC-3 prostate cancers. CONCLUSION: 18F-Al labeled exendin-4 analog might be a promising tracer for in vivo detecting GLP-1R positive prostate cancer with the advantage of facile synthesis and favorable pharmacokinetics. It may be useful in differential diagnosis, molecularly targeted therapy and prognosis of the cancers.

Targeting HER2-positive gastric cancer with a novel 18F-labeled ZHER2:342 probe.

To realize the diagnosis of HER2-positive gastric cancer via PET imaging, herein, a new kind of 18F-labeled HER2 affibody probe was created; the bifunctional maleimide derivative 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-MAL) was first coupled to a polypeptide, and the resulting compound was subsequently labeled with the 18FAl complex. The binding characteristics of the probe were assessed using both in vitro studies and in vivo microPET imaging and biodistribution experiments. Immunohistochemical staining was performed to confirm the expression level of HER2 in the studied cell lines and tumors. The probe was successfully produced with the radiochemical purity of more than 95%. The NCI N87 cell-associated radioactivity was 19.31 ± 1.01% AD, and it decreased to 0.83 ± 0.04% AD per 106 cells after blocking HER2 as early as 15 minutes post-incubation (p < 0.05). A competition binding assay between radiolabeled and non-radioactive affibody molecules with NCI N87 indicated that the IC50 was 8.10 nM. The microPET imaging and biodistribution of human gastric cancer xenografts demonstrated that the probe could specifically accumulate in tumors at early time points. Protein detection confirmed a strong HER2 expression in NCIN87 and a weak HER2 expression in SGC7901. In conclusion, 18FAl-NOTA-MAL-Cys-GGGRDN(M0)-ZHER2:342 was successfully prepared via a one-step method. The favorable preclinical data showed specific and effective tumor targeting capacity of the proposed probe; this revealed that the probe proposed herein might have potential application in gastric cancer imaging.

PET of HER2 Expression with a Novel 18FAl Labeled Affibody.

Background: Human epidermal growth factor receptor type 2 (HER2) is abundant in a wide variety of tumors and associated with the poor prognosis. Radiolabeled affibodies are potential candidates for detecting HER2-positive lesions. However, laborious multiple-step synthetic procedure and high abdomen background may hinder the widespread use. Herein, cysteinylated ZHER2:342 modified with a new hydrophilic linker (denoted as MZHER2:342) was designed and labeled using 18FAl-NOTA strategies. The biologic efficacy of the novel tracer and its feasibilities for in vivo monitoring HER2 levels were also investigated in xenograft models with different HER2 expressions. Method: MZHER2:342 was conjugated with MAL-NOTA under standard reaction conditions. The affibody molecule was then radiolabeled with 18FAl complex. The binding specificity of the tracer, 18FAl-NOTA-MAL-MZHER2:342, with HER2 was primarily characterized via in vitro studies. MicroPET imaging were performed in nude mice bearing tumors (SKOV-3, JIMT-1 and MCF-7) after injection. The HER2 levels of xenografts were determined using Western blotting analysis. Results:18FAl-NOTA-MAL-MZHER2:342 can be efficiently produced within 30 min with a non-decaycorrected yield of about 10% and a radiochemical purity of more than 95%. In vitro experiments revealed that the modified affibody retained the specific affinity to HER2. PET imaging showed that SKOV-3 and JIMT-1 xenografts were clearly visualized with excellent contrast and low abdomen backgrounds. On the contrary, the signals of MCF-7 tumor were difficult to visualize. The ROI values ranged from16.54±2.69% ID/g for SKOV-3 to 8.42±1.20 %ID/g for JIMT-1 tumors at 1h postinjection respectively. Poor uptake was observed from MCF-7 tumors with 1.71±0.34% ID/g at the same time point. Besides, a significant linear correlation between % ID/g values and relative HER2 expression levels was also found. Conclusions:18FAl-NOTA-MAL-MZHER2:342 is a promising tracer for in vivo detecting HER2 status with the advantages of facile synthesis and favorable pharmacokinetics. It may be useful in differential diagnosis, molecularly targeted therapy and prognosis of the cancers.

An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK.

A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates.

[Correlation between androgen receptor expression and hepatitis B virus X protein and its clinical significance in hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of androgen receptor (AR) and hepatitis B virus X protein (HBx) in hepatocellular carcinoma (HCC), and analyze the relationship between AR and HBx expressions. METHODS: Tumor tissues and peritumoral tissues of 83 HBV-associated HCC cases were investigated in this study. Fourteen cases of HBV-negative HCC and 13 cases of hemangioma peritumoral tissues were considered as control. AR and HBx mRNA levels were determined by quantitative fluorescence real-time RT-PCR and their protein levels were assayed by Western blot. The expression of AR and HBx proteins in tissues were examined with EnVision immunohistochemical staining. The methylation status of AR promoter was determined using methylation-specific PCR (MSP). RESULTS: Both expression levels of AR mRNA and protein of the peritumoral tissues were significantly higher (0.17) than that of tumor tissues (0.09) in HBV-associated HCC (P < 0.01), but such a difference was not found in HBV-negative HCC (0.06 vs. 0.07, P > 0.05). The level of AR expression in peritumoral tissues was associated with tumor differentiation in HBV-associated HCC. AR mRNA and protein levels of peritumoral tissues in HBV-associated HCC were significantly higher than that in HBV-negative HCC and hemangioma (all P < 0.05). In the tumor tissues, HBV-associated HCC had significantly higher AR expression than HBV-negative HCC at mRNA level (P < 0.05), but not at protein level. Spearman rank correlation analysis showed that the AR mRNA or AR protein levels were positively correlated with HBx in both tumor and peritumoral tissues in HBV-associated HCC, but the expressions of AR and HBx were not associated with AR promoter methylation status. The relative expression levels of AR mRNA and protein in the HBV-associated peritumoral tissues were negatively correlated with tumor differentiation (r = -0.213, P < 0.05; r = -0.313, P < 0.05), the higher the AR expression, the poorer differentiation. But this correlation of AR mRNA and protein was not shown in the hepatocellular carcinoma tissues. CONCLUSIONS: HBx may enhance AR expression in HBV-associated HCC, but AR promoter demethylation maybe not been involved in its main mechanism. An increased AR expression is probably an early event during the development and progression of HBV-associated HCC, and AR expression in the peritumoral tissue is correlated with HBV-associated HCC differentiation. AR may play different roles in HBV-associated HCC and HBV-negative HCC.