Real-time dose measurement in minibeam radiotherapy using radioluminescence imaging.

Purpose: Minibeam radiotherapy (MBRT) uses small parallel beams of radiation to create a highly modulated dose pattern. The aim of this study is to develop an optical radioluminescence imaging (RLI) approach to perform real-time dose measurement for MBRT.

Methods: MBRT was delivered using an image-guided small animal irradiator equipped with a custom collimator.

Combination of US hyperthermia and radiotherapy on a preclinical glioblastoma model.

In this work the effect of combining ultrasound (US) hyperthermia (HT) with radiotherapy (RT) was investigated. The treatment was applied to a GBM xenograft nude mouse model obtained by injecting U87 luc+ cells. The combined treatment group received 6 Gy and HT at for 8 min.

Cytotoxicity of PEG-Coated Gold and Gold-Iron Alloy Nanoparticles: ROS or Ferroptosis?

Nanomedicine relies on the exploitation of nanoscale constructs for therapeutic and diagnostic functions. Gold and gold-iron alloy nanoparticles (NPs) are two examples of nanomaterials with favorable features for use in nanomedicine. While gold NPs have been studied extensively in the last decades, they are not biodegradable.

From Nanothermometry to Bioimaging: Lanthanide-Activated KYF Nanostructures as Biocompatible Multifunctional Tools for Nanomedicine.

Lanthanide-activated fluoride-based nanostructures are extremely interesting multifunctional tools for many modern applications in nanomedicine, e.g., bioimaging, sensing, drug delivery, and photodynamic therapy.

Radioluminescence imaging feasibility for robotic radiosurgery field size quality assurance.

Purpose: To investigate the feasibility of radioluminescence imaging (RLI) as a novel 2D quality assurance (QA) dosimetry system for CyberKnife®.

Methods: We developed a field size measurement system based on a commercial complementary metal oxide semiconductor (CMOS) camera facing a radioluminescence screen located at the isocenter normal to the beam axis. The radioluminescence light collected by a lens was used to measure 2D dose distributions.

Tc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer.

Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC.

Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was Tc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations.

Photon emission and changes in fluorescent properties of bone after laser irradiation.

Laser scalpels used in medical surgery concentrate light energy, heating the tissues. Recently, we reported thermoluminescence emission from laser-treated soft tissues. Here we investigated the thermo-optical effects caused by a laser operating at 808 nm on animal bones (beef ribs) through luminescence and fluorescence imaging, thermal imaging and scanning electron microscopy.

Pre-clinical Research on Bladder Toxicity After Radiotherapy for Pelvic Cancers: State-of-the Art and Challenges.

Despite the dramatic advancements in pelvic radiotherapy, urinary toxicity remains a significant side-effect. The assessment of clinico-dosimetric predictors of radiation cystitis (RC) based on clinical data has improved substantially over the last decade; however, a thorough understanding of the physiopathogenetic mechanisms underlying the onset of RC, with its variegated acute and late urinary symptoms, is still largely lacking, and data from pre-clinical research is still limited. The aim of this review is to provide an overview of the main open issues and, ideally, to help investigators in orienting future research.

A non-invasive ultrasound imaging method to measure acute radiation-induced bladder wall thickening in rats.

Background: Methods for the non-invasive quantification of changes in bladder wall thickness as potential predictors of radiation cystitis in pre-clinical research would be desirable. The use of ultrasound for this aim seems promising, but is still relatively unexplored. A method using ultrasound for bladder wall thickness quantification in rats was developed and applied to measure early radiation-induced bladder wall thickness changes.

Nanoparticles for Cerenkov and Radioluminescent Light Enhancement for Imaging and Radiotherapy.

Cerenkov luminescence imaging and Cerenkov photodynamic therapy have been developed in recent years to exploit the Cerenkov radiation (CR) generated by radioisotopes, frequently used in Nuclear Medicine, to diagnose and fight cancer lesions. For in vivo detection, the endpoint energy of the radioisotope and, thus, the total number of the emitted Cerenkov photons, represents a very important variable and explains why, for example, Ga is better than F. However, it was also found that the scintillation process is an important mechanism for light production.

4D Multimodal Nanomedicines Made of Nonequilibrium Au-Fe Alloy Nanoparticles.

Several examples of nanosized therapeutic and imaging agents have been proposed to date, yet for most of them there is a low chance of clinical translation due to long-term retention and toxicity risks. The realization of nanoagents that can be removed from the body after use remains thus a great challenge. Here, we demonstrate that nonequilibrium gold-iron alloys behave as shape-morphing nanocrystals with the properties of self-degradable multifunctional nanomedicines.

Tandem Dye-Doped Nanoparticles for NIR Imaging via Cerenkov Resonance Energy Transfer.

The detection of the Cerenkov radiation (CR) is an emerging preclinical imaging technique which allows monitoring the distribution of radionuclides. Among its possible advantages, the most interesting is the simplicity and cost of the required instrumentation compared, e.g.

Small animal irradiator dose distribution verification using radioluminescence imaging.

The main objective of this work was the development of a novel 2D dosimetry approach for small animal external radiotherapy using radioluminescence imaging (RLI) with a commercial complementary metal oxide semiconductor detector. Measurements of RLI were performed on the small animal image-guided platform SmART, RLI data were corrected for perspective distortion using Matlab. Four irradiation fields were tested and the planar 2D dose distributions and dose profiles were compared against dose calculations performed with a Monte Carlo based treatment planning system and gafchromic film.

Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion.

Altered macrophage infiltration upon tissue damage results in inadequate healing due to inappropriate remodeling and stem cell recruitment and differentiation. We investigated whether cells of endothelial origin phenotypically change upon heterotopic ossification induction and whether infiltration of innate immunity cells influences their commitment and alters the ectopic bone formation. Liposome-encapsulated clodronate was used to assess macrophage impact on endothelial cells in the skeletal muscle upon acute damage in the ECs specific lineage-tracing Cdh5CreER:R26REYFP/dtTomato transgenic mice.

Weak biophoton emission after laser surgery application in soft tissues: Analysis of the optical features.

Nowadays, laser scalpels are commonly used in surgery, replacing the traditional surgical scalpels for several applications involving cutting or ablating living biological tissue. Laser scalpels are generally used to concentrate light energy in a very small-sized area; light energy is then converted in heat by the tissues. In other cases, the fiber glass tip of the laser scalpel is heated to high temperature and used to cut the tissues.

T-cell tracking using Cerenkov and radioluminescence imaging.

Cancer immunotherapy is a promising strategy based on the ability of the immune system to kill selected cells. In the development of an effective T-cell therapy, the noninvasive cell tracking methods play a crucial role. Here, we investigate the potentialities of T-cell marked with radionuclides in order to detect their localization with imaging techniques in small animal rodents.

Weak light emission of soft tissues induced by heating.

The main goal of this work is to show that soft tissue interaction with high-intensity focused ultrasound (HIFU) or direct heating leads to a weak light emission detectable using a small animal optical imaging system. Our results show that the luminescence signal is detectable after 30 min of heating, resembling the time scale of delayed luminescence. The imaging of a soft tissue after heating it using an HIFU field shows that the luminescence pattern closely matches the shape of the cone typical of the HIFU beam.

Radioluminescence from Tc-99m in glass predicts local dose.

The widely-used gamma-emitter Tc-99m has been shown to lead to optical emissions in mice and glass. We investigated the possibility that these emissions are due to the Cerenkov effect and whether the light emitted is proportional to local dose. By using a Geant4 Monte Carlo model matched to an experimental measurement, we show that the light detected by a small animal optical imaging system provides a 2D map of the dose throughout a glass sample.

Theranostic Role of P-ATP as Radiopharmaceutical for the Induction of Massive Cell Death within Avascular Tumor Core.

Drug inaccessibility to vast areas of the tumor parenchyma is amongst the major hurdles for conventional therapies. Treatment efficacy rapidly decreases with distance from vessels and most of the tumor cells survive therapy. Also, between subsequent cycles of treatment, spared cancer cells replace those killed near the vessels, improving their access to nutrients, boosting their proliferation rate, and thus enabling tumor repopulation.

Optical emission of Radium: in vitro and in vivo preclinical applications.

Radium ( Ra) is widely used in nuclear medicine to treat patients with osseous metastatic prostate cancer. In clinical practice Ra cannot be imaged directly; however, gamma photons produced by its short-lived daughter nuclides can be captured by conventional gamma cameras. In this work, we show that Ra and its short-lived daughter nuclides can be detected with optical imaging techniques.

Monte Carlo simulations support non-Cerenkov radioluminescence production in tissue.

There is experimental evidence for the production of non-Cerenkov radioluminescence in a variety of materials, including tissue. We constructed a Geant4 Monte Carlo simulation of the radiation from P32 and Tc99m interacting in chicken breast and used experimental imaging data to model a scintillation-like emission. The same radioluminescence spectrum is visible from both isotopes and cannot otherwise be explained through fluorescence or filter miscalibration.

Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery.

We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of 90Y-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory.

High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.

The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process.

Bremsstrahlung radiation detection for small animal imaging using a CCD detector.

The use of optical methods for the detection of radionuclides is becoming an established tool for preclinical molecular imaging experiments. In this paper we present a set of proof of principle experiments showing that planar bremsstrahlung radiation images can be detected with an intensifying screen using a small animal optical imager based on charge coupled device detector. We develop a bremsstrahlung source using a (32)P-ATP vial placed in a Plexiglas box, the source with an intensifying screen on top was placed inside a small animal optical imaging system.