High Pressure Nebulization (PIPAC) Versus Injection for the Intraperitoneal Administration of mRNA Complexes.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is hypothesized to have advantages such as enhancing tissue uptake, distributing drugs homogeneously within the closed and expanded abdominal cavity and higher local concentration of drugs in the peritoneal cavity. However, the clinical trials of PIPAC so far are limited to liquid chemotherapeutic solution, and the applicability of biomolecules (such as mRNA, siRNA and oligonucleotide) is not known.

Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure.

Hepatocellular carcinoma (HCC) is characterized by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which activates the unfolded protein response (UPR). However, the role of ER stress in tumor initiation and progression is controversial. To determine the impact of ER stress, we applied tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties.

Modulation of the unfolded protein response impedes tumor cell adaptation to proteotoxic stress: a PERK for hepatocellular carcinoma therapy.

Background: Functional disturbances of the endoplasmic reticulum (ER) lead to activation of the unfolded protein response (UPR), which is involved in the consecutive steps of carcinogenesis. In human hepatocellular carcinoma (HCC), the UPR is shown to be activated; however, little is known about the UPR kinetics and effects of UPR modulation in HCC.

Methods: We sequentially monitored the UPR over time in an orthotopic mouse model for HCC and explored the effects of UPR modulation on cell viability and proliferation in vitro and in the mouse model.

Therapeutic effects of artesunate in hepatocellular carcinoma: repurposing an ancient antimalarial agent.

Objectives: Artemisinins are antimalarial drugs that exert potent anticancer activity. We evaluated the effects of artesunate, a semisynthetic derivative of artemisinin, on tumor growth, angiogenesis, the unfolded protein response, and chemoresistance in hepatocellular carcinoma.

Materials And Methods: The effect of artesunate was examined in HepG2 and BWTG3 cells under normoxic and hypoxic conditions and in a diethylnitrosamine-induced mouse model.

Low-dose micro-CT imaging for vascular segmentation and analysis using sparse-view acquisitions.

The aim of this study is to investigate whether reliable and accurate 3D geometrical models of the murine aortic arch can be constructed from sparse-view data in vivo micro-CT acquisitions. This would considerably reduce acquisition time and X-ray dose. In vivo contrast-enhanced micro-CT datasets were reconstructed using a conventional filtered back projection algorithm (FDK), the image space reconstruction algorithm (ISRA) and total variation regularized ISRA (ISRA-TV).

Improved quantification in pinhole gated myocardial perfusion SPECT using micro-CT and ultrasound information.

Absolute quantification using single photon emission computed tomography (SPECT) was demonstrated in vitro and in large immobile organs in vivo. To determine the feasibility of in vivo quantification of myocardial perfusion in pinhole gated SPECT, we added an ultrasound derived partial volume correction factor to attenuation and scatter corrections, in combination with gated acquisitions. In nine male Wistar rats, cardiac ultrasound was performed prior to SPECT/CT scans to determine the myocardial wall thickness.

Regional quantitative analysis of small animal myocardial sympathetic innervation and initial application in streptozotocin induced diabetes.

Background: In several disease models it is known that heterogeneous dysinnervation occurs in the sympathetic nervous system. We therefore adapted the (123)I-MIBG imaging procedure in small animals to allow quantification of both global and regional uptake and wash-out rate using high specific activity (123)I-MIBG in the myocardium of rats. After evaluation of the image procedure in normal animals, we then applied our imaging protocol to visualize the regional dysinnervation in cardiac autonomic neuropathy occurring in streptozotocin-induced diabetes.

Longitudinal assessment of parotid function in patients receiving tomotherapy for head-and-neck cancer.

Background And Purpose: Conventional radiotherapy is associated with high doses to the salivary glands which causes xerostomia and adverse effects on quality of life. The study aims to investigate the potential of helical tomotherapy (Hi-Art Tomotherapy) to preserve parotid function in head-and-neck cancer patients.

Patients And Methods: Seven consecutive patients treated with helical tomotherapy at the UZ Brussel, Belgium, were included.

SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression.

Purpose: Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnostics and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody, for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice.

Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of D: -luciferin: effect on intensity, time kinetics and repeatability of photon emission.

Introduction: In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. D: -luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal.

Intramyocardial Implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT.

Unlabelled: Cell therapy-induced changes in the perfusion of areas of myocardial infarction (MI) remain unclear. This study investigated whether an original pinhole SPECT technique could be applied to a rat MI model to analyze local improvement in myocardial perfusion relating to engraftment sites of bone marrow-derived stem cells (BMSCs).

Methods: Four-month-old MI rats were either untreated (n = 8) or treated (n = 10) by intramyocardial injection of (111)In-labeled BMSCs.

123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients.

Purpose: 123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients.

Feasibility of in vivo dual-energy myocardial SPECT for monitoring the distribution of transplanted cells in relation to the infarction site.

Purpose: Cell therapy using bone marrow mesenchymal stem cells (BMSCs) shows promise in the treatment of myocardial infarction (MI) but accurate cell delivery within MI areas remains critical. In the present study, we tested the feasibility of in vivo pinhole SPECT imaging for monitoring the sites of intramyocardial implanted BMSCs in relation to targeted MI areas in rats.

Methods: BMSCs were labelled with (111)In-oxine and injected within the fibrotic areas of 3-month-old MI in ten rats.

Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study.

Unlabelled: The rat infarct model is widely used to study left ventricular (LV) remodeling, a main cause of heart failure characterized by progressive LV dilatation. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The aim of this study was to assess this new imaging technique for predicting and quantifying variable LV remodeling from the rat infarct model.

OSEM reconstruction, associated with temporal fourier and depth-dependant resolution recovery filtering, enhances results from sestamibi and 201Tl 16-interval gated SPECT.

Unlabelled: Gated SPECT recorded with 16 intervals determines left ventricular (LV) ejection fraction more accurately than does gated SPECT recorded with 8 intervals but produces higher image noise. This study aimed to assess the results from sestamibi and (201)Tl 16-interval gated SPECT when both signal-to-noise ratio and spatial resolution were enhanced with an original method of reconstruction.

Methods: Forty patients with coronary artery disease underwent (201)Tl and sestamibi 16-interval gated SPECT and, to be used as a reference, cardiac MRI.