Validation of the GATE Monte Carlo simulation platform for modelling a CsI(Tl) scintillation camera dedicated to small animal imaging

Monte Carlo simulations are increasingly used in scintigraphic imaging to model imaging systems and to develop and assess tomographic reconstruction algorithms and correction methods for improved image quantitation. GATE (GEANT 4 Application for Tomographic Emission) is a new Monte Carlo simulation platform based on GEANT4 dedicated to nuclear imaging applications. This paper describes the GATE simulation of a prototype of scintillation camera dedicated to small animal imaging and consisting of a CsI(Tl) crystal array coupled to a position sensitive photomultiplier tube. The relevance of GATE to model the camera prototype was assessed by comparing simulated 99mTc point spread functions, energy spectra, sensitivities, scatter fractions and image of a capillary phantom with the corresponding experimental measurements. Results showed an excellent agreement between simulated and experimental data: experimental spatial resolutions were predicted with an error less than 100 mu m. The difference between experimental and simulated system sensitivities for different source-to-collimator distances was within 2%. Simulated and experimental scatter fractions in a [98-182 keV] energy window differed by less than 2% for sources located in water. Simulated and experimental energy spectra agreed very well between 40 and 180 keV. These results demonstrate the ability and flexibility of GATE for simulating original detector designs. The main weakness of GATE concerns the long computation time it requires: this issue is currently under investigation by the GEANT4 and the GATE collaboration

Radiomics and Machine Learning for Skeletal Muscle Injury Recovery Prediction

Injuries; Muscles; RadiomicsLesions; Músculs; RadiòmicaLesiones; Músculos; RadiómicaRadiomics as a novel quantitative approach to medical imaging is an emerging area in the field of radiology. Artificial intelligence offers promising tools for exploiting and analyzing radiomics. The objective of the present study is to propose a methodology for the design, development, and evaluation of machine learning (ML) models for the prediction of the recovery progress of skeletal muscle injury over time in rats using radiomics. Radiomics were extracted from contrast enhanced computed tomography (CT) data and ML algorithms were trained and compared for their predictive value based on different CT imaging parameters. Ten different ML regression algorithms were tested and the optimal combination of radiomics for each algorithm and CT imaging parameter settings combination was studied. The best ensemble learning model, trained on the 70 kVp, 100 mA imaging parameter dataset, achieved a mean absolute error score of 1.22. The results suggest that radiomics extracted from CT images can be used as input in ML regression algorithms to predict the volume of a skeletal muscle injury in rats. Moreover, the results show that CT imaging settings impact the predictive performance of the ML regression models, indicating that lower values of tube current and peak kilovoltage contribute to more accurate predictions.10.13039/100010671-European Union’s Horizon Research and Innovation Program (Grant Number: 761031

In vitro cell interaction and in vivo biodistribution of poly (dl-lactide-co-glycolide) nanospheres with encapsulated selenium nanoparticles for the treatment of liver diseases

The role of selenium as a chemopreventive and chemotherapeutic agent has been supported by a large number of epidemiological, preclinical, and clinical trials [1, 2] suggesting that anti-tumor effect mechanisms of selenium include induction of apoptosis, inhibition of cell proliferation, protection against oxidative stress, and stimulation of immune system. Herein we demonstrate a simple and quick synthesis of uniform, stable, amorphous selenium nanoparticles (SeNps), using ascorbic acid as the reduction agent. The choice of an appropriate stabilizer and reducing agent for preparation of stable selenium nanoparticles is very important. We used bovine serum albumin (BSA) as an organic layer for selenium nanoparticles, i.e., as a capping agent to make them more biocompatibile and protect them from agglomeration in the suspension medium. SeNps were additionally encapsulated within spherical PLGA particles (PLGA/SeNps). One of the most important requirements for the controlled and balanced release of the drug in the body is ideal spherical shape of the particles and narrow distribution of their sizes. The morphology (size and shape) of the particles plays key role in their adhesion and interaction with the cell. The influence of PLGA/SeNps on cell viability, ROS generation in HepG2 cells, as well as anticancer activity against epithelial tumor cells was investigated. Synthesized nanoparticles were characterized by FTIR spectroscopy, FESEM, TEM, HRTEM, and Zeta potential measurements. As a part of this study, we have also performed in vivo dynamic imaging studies in normal mice, using SPECT imaging and a high resolution gamma camera. The PLGA/SeNps nanoparticles have been radiolabelled with Tc-99m, by applying the direct labeling method [3]. Ex vivo biodistribution measurements, as well as in vivo dynamic studies up to 1h p.i. and at 24h were performed, showing increased concentration in liver and spleen. Acknowledgements This study was supported by the Ministry of Science and Technological Development of the Republic of Serbia, under Grant No. III45004: Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them. Presented were the results of a study also supported by the COST Action TD1004. References 1. Popova, N. V. Cancer Lett. 2002, 179, 39–42. 2. Li, S.; Zhou, Y.; Wang, R.; Zhang, H.; Dong, Y.; Ip, C. Mol. Cancer Ther. 2007, 6, 1031–1038. 3. Psimadas, D.; Baldi, G.; Ravagli, C.; Bouziotis, P.; Xanthopoulos, S.; Francini, M.; Georgoulias, P.; Loudos, G.; J. Biom. Nan., 2012, 8, 4, 575-585

Poly (DL-lactide-co-glycolide) nanospheres with encapsulated selenium nanoparticles as a system with therapeutic functionality

Selenium (Se) is an essential trace element with important physiological functions and extensive pharmacological actions. The role of selenium as a chemopreventive and chemotherapeutic agent has been supported by a large number of epidemiological, preclinical, and clinical trials. Uniform, stable, amorphous selenium nanoparticles (SeNps) have been synthesized and additionally encapsulated within spherical PLGA particles (PLGA/SeNps). The morphology (size and shape) of the particles plays key role in their adhesion and interaction with the cell. Synthesized particles were characterized by FTIR spectroscopy, FESEM, TEM, HRTEM, and Zeta potential measurements. The influence of PLGA/SeNps on cell viability, ROS generation in HepG2 cells, as well as anticancer activity against epithelial tumor cells was investigated. As a part of this study, we have also performed in vivo dynamic imaging studies in normal mice, using SPECT imaging and a high resolution gamma camera. The PLGA/SeNps nanoparticles have been radiolabelled with Tc-99m, by applying the direct labeling method. Ex vivo biodistribution measurements, as well as in vivo dynamic studies up to 1h p.i. and at 24h were performed, showing increased concentration in liver and spleen

In vivo biodistribution of edelfosine-loaded lipid nanoparticles radiolabeled with Technetium-99 m: Comparison of administration routes in mice

Edelfosine (ET) is a potent antitumor agent but causes severe side effects that have limited its use in clinical practice. For this reason, nanoencapsulation in lipid nanoparticles (LNs) is advantageous as it protects from ET side-effects. Interestingly, previous studies showed the efficacy of LNs containing ET in various types of tumor. In this paper, biodistribution studies of nanoencapsulated ET, administered by three routes (oral, intravenous (IV) and intraperitoneal (IP)), were tested in order to select the optimal route of administration. To do this, ET-LNs were labeled with Technetium-99 m (99mTc) and administered by the oral, IV and IP route in mice. IV admin- istration of the radiolabeled LNs led to fast elimination from the blood circulation and increased accumulation in reticulo-endothelial (RES) organs, while their oral administration could not provide any evidence on their bio- distribution since large radiocomplexes were formed in the presence of gastrointestinal fluids. However, when the LNs were administered by the IP route they could access the systemic circulation and provided more constant blood ET-LN levels compared to the IV route. These findings suggest that the IP route can be used to sustain the level of drug in the blood and avoid accumulation in RES organs

In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles

Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with (99m)Tc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line. Following radiolabeling with (99m)Tc, the biodistribution and therapeutic hyperthermic effects of the nanosystem were studied noninvasively in vivo in tumor-bearing mice. A substantial decrease in tumor size correlated with an increase in both nanoparticle concentration and local temperature was achieved, confirming the possibility of using this multifunctional nanosystem as a therapeutic tool for epidermoid carcinoma

'Brukin2D' : a 2D visualization and comparison tool for LC-MS data

Peer reviewe

On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99mTc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications. STATEMENT OF SIGNIFICANCE: The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging

One step closer to clinical translation: Enhanced tumor targeting of [99mTc]Tc-DB4 and [111In]In-SG4 in mice treated with entresto

Background: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibit