Three-Dimensional-Bioprinted Non-Small Cell Lung Cancer Models in a Mouse Phantom for Radiotherapy Research.

Lung cancer continues to have one of the highest morbidity and mortality rates of any cancer. Although radiochemotherapy, in combination with immunotherapy, has significantly improved overall survival, new treatment options are urgently needed. However, preclinical radiotherapy testing is often performed in animal models, which has several drawbacks, including species-specific differences and ethical concerns.

3D Imaging of Striatal Transplants in a Small Animal Model of Huntington's Disease.

High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington's disease. Four adult female Sprague Dawley rats each received injections of 0.

A Novel Anthropomorphic Phantom Composed of Tissue-Equivalent Materials for Use in Experimental Radiotherapy: Design, Dosimetry and Biological Pilot Study.

The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy.

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model.

Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy.

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction.

Background: High-dose-rate radiotherapy has shown promising results with respect to normal tissue preservation. We developed an ex vivo model to study the physiological effects of experimental radiotherapy in the rodent esophageal smooth muscle.

Methods: We assessed the physiological parameters of the esophageal function in ex vivo preparations of the proximal, middle, and distal segments in the organ bath.

Good Timing Matters: The Spatially Fractionated High Dose Rate Boost Should Come First.

Monoplanar microbeam irradiation (MBI) and pencilbeam irradiation (PBI) are two new concepts of high dose rate radiotherapy, combined with spatial dose fractionation at the micrometre range. In a small animal model, we have explored the concept of integrating MBI or PBI as a simultaneously integrated boost (SIB), either at the beginning or at the end of a conventional, low-dose rate schedule of 5x4 Gy broad beam (BB) whole brain radiotherapy (WBRT). MBI was administered as array of 50 µm wide, quasi-parallel microbeams.

The Microbeam Insert at the White Beam Beamline P61A at the Synchrotron PETRA III/DESY: A New Tool for High Dose Rate Irradiation Research.

High dose rate radiotherapies such as FLASH and microbeam radiotherapy (MRT) both have developed to the stage of first veterinary studies within the last decade. With the development of a new research tool for high dose rate radiotherapy at the end station P61A of the synchrotron beamline P61 on the DESY campus in Hamburg, we increased the research capacity in this field to speed up the translation of the radiotherapy techniques which are still experimental, from bench to bedside. At P61, dose rates of several hundred Gy/s can be delivered.

Evaluating the Suitability of 3D Bioprinted Samples for Experimental Radiotherapy: A Pilot Study.

Radiotherapy is an important component in the treatment of lung cancer, one of the most common cancers worldwide, frequently resulting in death within only a few years of diagnosis. In order to evaluate new therapeutic approaches and compare their efficiency with regard to tumour control at a pre-clinical stage, it is important to develop standardized samples which can serve as inter-institutional outcome controls, independent of differences in local technical parameters or specific techniques. Recent developments in 3D bioprinting techniques could provide a sophisticated solution to this challenge.

Microbeam Irradiation as a Simultaneously Integrated Boost in a Conventional Whole-Brain Radiotherapy Protocol.

Microbeam radiotherapy (MRT), an experimental high-dose rate concept with spatial fractionation at the micrometre range, has shown a high therapeutic potential as well as good preservation of normal tissue function in pre-clinical studies. We investigated the suitability of MRT as a simultaneously integrated boost (SIB) in conventional whole-brain irradiation (WBRT). A 174 Gy MRT SIB was administered with an array of quasi-parallel, 50 µm wide microbeams spaced at a centre-to-centre distance of 400 µm either on the first or last day of a 5 × 4 Gy radiotherapy schedule in healthy adult C57 BL/6J mice and in F98 glioma cell cultures.

Modification of the Langendorff system of the isolated beating heart for experimental radiotherapy at a synchrotron: 4000 Gy in a heart beat.

Microbeam radiotherapy could help to cure malignant tumours which are currently still considered therapy-resistant. With an irradiation target in the thoracic cavity, the heart would be one of the most important organs at risk. To assess the acute adverse effects of microbeam irradiation in the heart, a powerful ex vivo tool was created by combining the Langendorff model of the isolated beating mammalian heart with X-Tream dosimetry.

Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function.

Purpose: Microbeam radiation therapy (MRT) has shown several advantages compared with conventional broad-beam radiation therapy in small animal models, including a better preservation of normal tissue function and improved drug delivery based on a rapidly increased vascular permeability in the target region. Normal tissue tolerance is the limiting factor in clinical radiation therapy. Knowledge of the normal tissue tolerance of organs at risk is therefore a prerequisite in evaluating any new radiation therapy approach.

Flying rats and microbeam paths crossing: the beauty of international interdisciplinary science.

Purpose: Microbeam radiotherapy (MRT) is a still experimental radiotherapy approach. Two combined parameters contribute to an excellent normal tissue protection and an improved control of malignant tumors in small animal models, compared to conventional radiotherapy: dose deposition at a high dose rate and spatial fractionation at the micrometre level. The international microbeam research community expects to see clinical MRT trials within the next ten years.

The radioenhancement potential of Schiff base derived copper (II) compounds against lung carcinoma in vitro.

For the last years, copper complexes have been intensively implicated in biomedical research as components of cancer treatment. Herewith, we provide highlights of the synthesis, physical measurements, structural characterization of the newly developed Cu(II) chelates of Schiff Bases, Cu(Picolinyl-L-Tryptopahanate)2, Cu(Picolinyl-L-Tyrosinate)2, Cu(Isonicotinyl-L-Tyrosinate)2, Cu(Picolinyl-L-Phenylalaninate)2, Cu(Nicotinyl-L-Phenylalaninate)2, Cu(Isonicotinyl-L-Phenylalaninate)2, and their radioenhancement capacity at kV and MV ranges of irradiation of human lung carcinoma epithelial cells in vitro. The methods of cell growth, viability and proliferation were used.

Perspectives for microbeam irradiation at the SYRMEP beamline.

It has been shown previously both in vitro and in vivo that microbeam irradiation (MBI) can control malignant tumour cells more effectively than the clinically established concepts of broad beam irradiation. With the aim to extend the international capacity for microbeam research, the first MBI experiment at the biomedical beamline SYRMEP of the Italian synchrotron facility ELETTRA has been conducted. Using a multislit collimator produced by the company TECOMET, arrays of quasi-parallel microbeams were successfully generated with a beam width of 50 µm and a centre-to-centre distance of 400 µm.

A Mouse Model for Microbeam Radiation Therapy of the Lung.

Purpose: Radiation therapy is an important treatment component for patients with lung cancer. However, the survival time gained with clinical radiation therapy techniques is relatively short. Data from preclinical experiments suggest that synchrotron microbeam radiation therapy could be much better suited to control malignant brain tumors than current clinical concepts of radiation therapy.

Perampanel Add-on to Standard Radiochemotherapy Promotes Neuroprotection in a Rodent F98 Glioma Model.

An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT).

Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus.

The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation.

Homogenous and Microbeam X-Ray Radiation Induces Proteomic Changes in the Brains of Irradiated Rats and in the Brains of Nonirradiated Cage Mate Rats.

To evaluate microbeam radiation therapy (MRT), for brain tumor treatment, the bystander effect in nonirradiated companion animals was investigated. Adult rats were irradiated with 35 or 350 Gy at the European Synchrotron Research Facility using homogenous irradiation (HR) or MRT to the right brain hemisphere. The irradiated rats were housed with nonirradiated rats.

Microbeam radiation therapy - grid therapy and beyond: a clinical perspective.

Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even though there is now a large number of animal studies demonstrating its marked therapeutic potential with an exceptional normal tissue sparing effect.

Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.

Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role.

SYRA3 COST Action--Microbeam radiation therapy: Roots and prospects.

Microbeam radiation therapy (MRT) is an irradiation modality for therapeutic purposes which uses arrays of collimated quasi parallel microbeams, each up to 100 μm wide, to deliver high radiation doses. Several studies have reported the extraordinary tolerance of normal tissues to MRT irradiation; conversely, MRT has been shown to be highly efficient on tumor growth control. The original and most widely developed application of MRT, yet in the preclinical phase, consists in using spatially fractionated X-ray beams issued from a synchrotron radiation source in the treatment of brain tumors.

Use of synchrotron medical microbeam irradiation to investigate radiation-induced bystander and abscopal effects in vivo.

The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile.

γ-H2AX as a marker for dose deposition in the brain of wistar rats after synchrotron microbeam radiation.

Objective: Synchrotron radiation has shown high therapeutic potential in small animal models of malignant brain tumours. However, more studies are needed to understand the radiobiological effects caused by the delivery of high doses of spatially fractionated x-rays in tissue. The purpose of this study was to explore the use of the γ-H2AX antibody as a marker for dose deposition in the brain of rats after synchrotron microbeam radiation therapy (MRT).

Transmission of signals from rats receiving high doses of microbeam radiation to cage mates: an inter-mammal bystander effect.

Inter-animal signaling from irradiated to non-irradiated organisms has been demonstrated for whole body irradiated mice and also for fish. The aim of the current study was to look at radiotherapy style limited exposure to part of the body using doses relevant in preclinical therapy. High dose homogenous field irradiation and the use of irradiation in the microbeam radiation therapy mode at the European Synchrotron Radiation Facility (ESRF) at Grenoble was tested by giving high doses to the right brain hemisphere of the rat.

Single-cell resolution in high-resolution synchrotron X-ray CT imaging with gold nanoparticles.

Gold nanoparticles are excellent intracellular markers in X-ray imaging. Having shown previously the suitability of gold nanoparticles to detect small groups of cells with the synchrotron-based computed tomography (CT) technique both ex vivo and in vivo, it is now demonstrated that even single-cell resolution can be obtained in the brain at least ex vivo. Working in a small animal model of malignant brain tumour, the image quality obtained with different imaging modalities was compared.