Intracellular Redox-Balance Involvement in Temozolomide Resistance-Related Molecular Mechanisms in Glioblastoma.

Glioblastoma (GBM) is the most common astrocytic-derived brain tumor in adults, characterized by a poor prognosis mainly due to the resistance to the available therapy. The study of mitochondria-derived oxidative stress, and of the biological events that orbit around it, might help in the comprehension of the molecular mechanisms at the base of GBM responsiveness to Temozolomide (TMZ). Sensitive and resistant GBM cells were used to test the role of mitochondrial ROS release in TMZ-resistance.

Hypoxia-Inducible Factor-1α Activity as a Switch for Glioblastoma Responsiveness to Temozolomide.

Rationale: The activity of the transcription factor, hypoxia-inducible factor (HIF)-1α, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1α is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ.

Methods: The effect of HIF-1α silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluating cell viability and apoptosis-related gene balance.

Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.

Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs) represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO)-generating enzyme inducible nitric oxide synthase (iNOS).

Impact of non-specific normal databases on perfusion quantification of low-dose myocardial SPECT studies.

Aim: To evaluate the impact of non-specific normal databases on the percent summed rest score (SR%) and stress score (SS%) from simulated low-dose SPECT studies by shortening the acquisition time/projection.

Methods: Forty normal-weight and 40 overweight/obese patients underwent myocardial studies with a conventional gamma-camera (BrightView, Philips) using three different acquisition times/projection: 30, 15, and 8 s (100%-counts, 50%-counts, and 25%-counts scan, respectively) and reconstructed using the iterative algorithm with resolution recovery (IRR) Astonish (Philips). Three sets of normal databases were used: (1) full-counts IRR; (2) half-counts IRR; and (3) full-counts traditional reconstruction algorithm database (TRAD).

Comparative analysis of iterative reconstruction algorithms with resolution recovery and new solid state cameras dedicated to myocardial perfusion imaging.

New technologies are available in myocardial perfusion imaging. They include new software that recovers image resolution and limits image noise, multifocal collimators and dedicated cardiac cameras in which solid-state detectors are used and all available detectors are constrained to imaging just the cardiac field of view. These innovations resulted in shortened study times or reduced administered activity to patients, while preserving image quality.

18F-FDG PET/CT in Bladder Cancer.

Urinary clearance of F-FDG and variability in bladder wall FDG uptake may hamper the interpretation and limit the use of FDG-PET/CT for imaging bladder tumors. Nevertheless, careful combined evaluation of both CT and FDG-PET images of the urinary tract can provide useful findings. We present 2 cases of bladder cancer detected by FDG-PET/CT.

Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming.

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia.

Differences in polar-map patterns using the novel technologies for myocardial perfusion imaging.

Background: New technologies are available in MPI. Our aim was to evaluate their impact on the uniformity of normal myocardial uptake in the polar-map representation, over different count statistics, with and without the attenuation (AC) and scatter corrections (SC).

Methods: A phantom study was performed using 5 Anger gamma cameras with filtered back projection or iterative reconstruction with resolution recovery (IRR), with or without SCAC; a D530c, with or without AC; and a D-SPECT.

Optical imaging probes in oncology.

Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions.

Comparative analysis of full-time, half-time, and quarter-time myocardial ECG-gated SPECT quantification in normal-weight and overweight patients.

Background: The introduction of a camera-based dose-reduction strategy in myocardial perfusion imaging (MPI) clinical setting entails the definition of objective and reproducible criteria for establishing the amount of activity to be injected.

Aim: The aim is to evaluate the impact of count statistics on the estimation of summed-scores (SS), end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF).

Methods: Data rest/stress ECG-gated SPECT (2-day protocol and 8 MBq·kg) were acquired with Bright View gamma camera and Astonish algorithm for 40 normal-weight and 40 overweight patients.

Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy.

Introduction: Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies.

Matherials & Methods: We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation.

In vivo imaging study of angiogenesis in a channelized porous scaffold.

The main scientific issue hindering the development of tissue engineering technologies is the lack of proper vascularization. Among the various approaches developed for boosting vascularization, scaffold design has attracted increasing interest over the last few years. The aim of this article is to illustrate a scaffold design strategy for enhancing vascularization based on sacrificial microfabrication of embedded microchannels.

Variability of [18F]FDG administered activities among patients undergoing PET examinations: an international multicenter survey.

Given the large number of [(18)F]fluorodeoxyglucose (FDG) PET examinations performed annually throughout the world, reduction of the administered activity without compromise of the clinical information being sought is encouraged. Guidelines issued by the SNMMI and European Association of Nuclear Medicine (EANM) differ greatly on the choice of the activity that should be administered to patients: the EANM suggests a personalised activity based on the patient's body weight, whereas the SNMMI recommends the administration of fixed activities. The authors analysed a database of 24 716 [(18)F]FDG administrations performed worldwide in 15 PET centres to assess the degree of heterogeneity, in relation to available technology, operational protocols and reference guidelines.

Correlation between 123I-FP-CIT brain SPECT and parkinsonism in dementia with Lewy bodies: caveat for clinical use.

Introduction: Although parkinsonism is considered a core feature of dementia with Lewy bodies (DLB), it is occasionally mild or even absent. I-FP-CIT SPECT has been accepted as a diagnostic support tool in this context, given that low striatal uptake is associated with neuronal loss. The aim of this retrospective study was to look for correlations between I-FP-CIT uptake in the striatum and clinical extrapyramidal signs (EPSs) in patients with a diagnosis of probable DLB to clarify the extent to which the supporting role of I-FP-CIT is related to motor impairment.

A reliable indirect cell-labelling protocol for optical imaging allows ex vivo visualisation of mesenchymal stem cells after transplantation.

We set out to assess the feasibility of exploiting expression of the mCherry gene, after lentiviral infection, in order visualise bone marrow-derived human mesenchymal stem cells (hMSCs) by optical imaging, and to provide proof of principle of this approach as a method for cell tracking and quantification in pre-clinical models. Commercial hMSCs were infected with a lentiviral vector carrying the mCherry gene under the control of the phosphoglycerate kinase promoter. After extensive in vitro culture, infected hMSCs were analysed for viability, morphology, differentiation capability, and maintenance of fluorescence.

Evaluation of renal function in elderly patients: performance of creatinine-based formulae versus the isotopic method using 99mTc-diethylene triamine pentaacetic acid.

Introduction: Measurement of the glomerular filtration rate (GFR) is recognized worldwide as the most accurate way of assessing kidney function. The prevalence of impaired renal function increases with advancing age. In this study we compared the clinical formulae Cockcroft-Gault (CG), isotope dilution mass spectrometry-modification of diet in renal disease (IMDS-MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) in elderly patients over and under the age of 70 years in an attempt to establish which formula produces the best measurement of renal function in this population.

Diagnosis and treatment of pulmonary embolism: a multidisciplinary approach.

The diagnosis of pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Although early treatment is highly effective, PE is underdiagnosed and, therefore, the disease remains a major health problem. Since symptoms and signs are non specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care.

Validation of a new protocol for ¹⁸F-FDG infusion using an automatic combined dispenser and injector system.

Purpose: In nuclear medicine, radiopharmaceuticals are usually administered in unit doses partitioned from multi-dose vials. The partitioning typically takes place in a radiopharmacy, depending on local practice. Automatic, as opposed to manual, partitioning and administration should reduce radiation exposure of the personnel involved, improve the accuracy of the administration and mitigate contamination.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer.

Aim: The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa).

Methods: In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately.

In vivo imaging of lymph node migration of MNP- and (111)In-labeled dendritic cells in a transgenic mouse model of breast cancer (MMTV-Ras).

Purpose: The authors present a protocol for the in vivo evaluation, using different imaging techniques, of lymph node (LN) homing of tumor-specific dendritic cells (DCs) in a murine breast cancer model.

Procedures: Bone marrow DCs were labeled with paramagnetic nanoparticles (MNPs) or (111)In-oxine. Antigen loading was performed using tumor lysate.

Labeling protocols for in vivo tracking of human skeletal muscle cells (HSkMCs) by magnetic resonance and bioluminescence imaging.

Purpose: We propose herein labeling protocols for multimodal in vivo visualization of human skeletal muscle cells (HSkMCs) by MRI and BLI to investigate the survival, localization, and proliferation/differentiation of these cells in cell-mediated therapy.

Procedures: HSkMCs were labeled with different quantities of Endorem® and transfection agents or infected with lentiviral vector expressing the luciferase gene under the myogenin promoter. Cells were evaluated before and after intra-arterial injection in NUDE mice with N₂-induced muscle inflammation.