Teacher evaluation in the Kingdom of Saudi Arabia's (KSA) schools - moving forward

The aim of this optimization study was to minimize the acquisition time of 68Ga-HBED-CC-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with local and metastatic prostate cancer (PCa) to obtain a sufficient image quality and quantification accuracy without any appreciable loss.Twenty patients with PCa were administered intravenously with the 68Ga-HBED-CC-PSMA ligand (mean activity 99 MBq/patient, range 76-148 MBq) and subsequently underwent PET/MRI at, on average, 168 min (range 77-320 min) after injection. PET and MR imaging data were acquired simultaneously. PET acquisition was performed in list mode and PET images were reconstructed at different time intervals (1, 2, 4, 6, 8, and 10 min). Data were analyzed regarding radiotracer uptake in tumors and muscle tissue and PET image quality. Tumor uptake was quantified in terms of the maximum and mean standardized uptake value (SUVmax, SUVmean) within a spherical volume of interest (VOI). Reference VOIs were drawn in the gluteus maximus muscle on the right side. PET image quality was evaluated by experienced nuclear physicians/radiologists using a five-point ordinal scale from 5-1 (excellent-insufficient).Lesion detectability linearly increased with increasing acquisition times, reaching its maximum at PET acquisition times of 4 min. At this image acquisition time, tumor lesions in 19/20 (95%) patients were detected. PET image quality showed a positive correlation with increasing acquisition time, reaching a plateau at 4-6 min image acquisition. Both SUVmax and SUVmean correlated inversely with acquisition time and reached a plateau at acquisition times after 4 min.In the applied image acquisition settings, the optimal acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic PCa was identified to be 4 min per bed position. At this acquisition time, PET image quality and lesion detectability reach a maximum while SUVmax and SUVmean do not change significantly beyond this time point

MR imaging sequence parameters.

<p>MR imaging sequence parameters.</p

PET images of a patient (age: 66 years, serum PSA: 2.3 ng/ml) with recurrent PCa in two iliacal lymph nodes obtained with the PET/MR hybrid imaging system at 134 min after intravenous injection of ⁶⁸Ga-HBED-CC-PSMA (146 MBq).

<p>a) Scatter und attenuation corrected PET images with intense ‘halo artifact’ showing only one iliacal lymph node. b) Non-scatter and attenuation corrected PET image showing both lymph nodes that were seen on PET/CT as well.</p

Image quality of ⁶⁸Ga-HBED-CC-PSMA PET/MRI of a patient with recurrent PCa in an ilical lymph node.

<p>Images were acquired at 3 h p.i.. Left panel: PET/MR fusion image, right panel: PET image of the PET/MR hybrid imaging system. Acquisition times were a) 1 min, b) 2 min, c) 3 min, d) 4 min, e) 6 min, f) 8 min, and g) 10 min. PET image quality rises with increasing acquisition times and reaches a plateau at an acquisition time of 4 min. The halo artifact first occurs at image acquisition times of 4 min.</p

Patient characteristics.

<p>Patient characteristics.</p

A novel approach to detect resistance mechanisms reveals FGR as a factor mediating HDAC inhibitor SAHA resistance in B-cell lymphoma

Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are not commonly used in clinical practice for treatment of B‐cell lymphomas, although a subset of patients with refractory or relapsed B‐cell lymphoma achieved partial or complete remissions. Therefore, the purpose of this study was to identify molecular features that predict the response of B‐cell lymphomas to SAHA treatment. We designed an integrative approach combining drug efficacy testing with exome and captured target analysis (DETECT). In this study, we tested SAHA sensitivity in 26 B‐cell lymphoma cell lines and determined SAHA‐interacting proteins in SAHA resistant and sensitive cell lines employing a SAHA capture compound (CC) and mass spectrometry (CCMS). In addition, we performed exome mutation analysis. Candidate validation was done by expression analysis and knock‐out experiments. An integrated network analysis revealed that the Src tyrosine kinase Gardner‐Rasheed feline sarcoma viral (v‐fgr) oncogene homolog (FGR) is associated with SAHA resistance. FGR was specifically captured by the SAHA‐CC in resistant cells. In line with this observation, we found that FGR expression was significantly higher in SAHA resistant cell lines. As functional proof, CRISPR/Cas9 mediated FGR knock‐out in resistant cells increased SAHA sensitivity. In silico analysis of B‐cell lymphoma samples (n = 1200) showed a wide range of FGR expression indicating that FGR expression might help to stratify patients, which clinically benefit from SAHA therapy. In conclusion, our comprehensive analysis of SAHA‐interacting proteins highlights FGR as a factor involved in SAHA resistance in B‐cell lymphoma