Preclinical nuclear molecular imaging speeds up the mean time from synthesis to market, in drug development process. Commercial imaging systems have in general high cost, require high-cost service ...contracts, special facilities and trained staff. In the current work, we present β-eye, a benchtop system for in vivo molecular screening of labeled compounds with Positron Emission Tomography (PET) isotopes. The developed system is based on a dual-head geometry, offering simplicity and decreased cost. The goal of the design is to provide 2D, real-time radionuclide images of mice, allowing the recording of fast frames and thus perform fast kinetic studies, with spatial resolution of ∼2 mm. Performance evaluation demonstrates the ability of β-eye to provide quantitative results for injected activities lower than 1.5 MBq, which is adequate for pharmacodynamic studies in small mice.
•Preclinical PET with dual head-based geometry, suitable for whole body mouse imaging.•Compact and cost-effective PET scanner based on PMTs and BGO scintillators.•2D real time imaging of radiolabeled compounds with any PET isotope.•Accurate and fast quantitative information in preclinical oncology studies.
For every new drug, >10,000 candidate molecules are tested for ~15 years. This is the daily mission of thousands research teams worldwide. It is well proven that small animal imaging speeds up this ...work, increases accuracy and decreases costs. However, commercial imaging systems have high purchase cost, require high service contracts, special facilities and trained staff. Thus, they are affordable to only few large research centres and not to the majority of small and medium research teams internationally. There are two main reasons that urge the addressing of this problem at large scale now: Firstly, small animal imaging started in 2000 and quickly research community and pharma industry understood its value, which opened preclinical imaging market (>2.5 Bil $). Continuous evolution in medicine and biology clearly shows the need to speed up research using new tools. Asian countries rapidly invest funds in drug research, enlarging existing market. Secondly, until recently such systems were based on complicated electronics and expensive components. Evolution in detector technology, electronics, software and 3D printing, made feasible the development of benchtop imaging systems, with attractive end user price.
Being an active partner of numerous international and national projects, we tried to identify the main requirements that an imaging system should have, in order to become a screening tool for daily use. Thus, we recently developed a new generation of affordable, but high-performance imaging systems, which can fulfil the daily needs of all research labs activated in preclinical research. Our technology covers the field of SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) imaging, while an optical and x-ray imaging system is under development. The systems are based on well tested technology, including pixeliated scintillators, Position Sensitive Photomultipliers, programmable ADCs (Analog to Digital Converters) and FPGAs (Field Programmable Gate Arrays) and are connected with a standard laptop through USB and Ethernet connection. The systems are named "eyes-series" and have been already tested for fast screening of small animals injected with labeled compounds including peptides, antibodies and nanoparticles. Besides their performance, they are offered at a fraction of the cost of the commercial ones, comparable to standard lab equipment such as HPLC, gamma counter etc, opening new prospects in preclinical research. The first system is called "γ-eye™" and it is a dedicated system for imaging photons (γ-rays) which are emitted from radiolabelled biomolecules (2D-SPECT). The second system is called "β-eye™" and detects positrons (β-rays) from similar biomolecules (2D-PET). They both have dimensions which are 35x35x30cm and weight which is less that 30kgr. The spatial resolution of both systems is <2mm and their energy resolution <20%. Their sensitivity allows real time imaging for the first second post injection, while images are shown in real time during acquisition. They allow recording of fast frames, down to 1min, thus it is possible to perform fast kinetic studies. Finally, they are both provided along with a laptop that has preinstalled the required software, named "VISUAL-eyes".
The technical specifications and performance evaluation of our technology will be presented. Different applications including oncology, regenerative medicine, nanomedicine and lung imaging will be given. Finally, the results of the comparison against high performance systems and a typical workflow for optimizing throughput will be demonstrated.
The operation of a compact and busy preclinical laboratory comes with many challenges but also presents some surprising opportunities. Running a mouse and rat animal facility and full laboratory with ...a procedures room, multiple imaging modalities, radiochemical and cells lab, in a 100 m2 space has proven very functional from a managerial, organizational and multitasking aspect, as everything and everyone is close and easy to coordinate. Space limitations mainly affect washing, waste and supplies storage, adding heavy big equipment such as a biosafety cabinet, and hosting staff and occasional visitors. Operating the animal facility necessitates thorough sterilizations of cages and equipment in order to avoid cross-contamination due to receipt of animals from different breeders and health status. Procedure rooms are strategically organized to fit many needs, with the help of modern compact experimental equipment. The all in - all out operation, ability of close supervision, proximity of all laboratories, and good collaboration of everyone involved overcomes the confined space and allows for a rather convenient workflow. Radioprotection is addressed by using appropriate equipment and organizing the work accordingly, and exposure limits can be kept to the minimum for the public (1 mSv/year). Our experience proves that with good organization, resourcefulness and teamwork, less is more!
The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer ...2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity (>91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that Ga68-Fe3O4-DPD MNPs could serve as an important diagnostic tool for biomedical imaging.
Schizophrenia is a severe mental disorder, characterized by profound disruptions in thinking, affecting language, perception, and the sense of self. Schizophrenia disorders manifest themselves early ...in life, affecting approximately 1% of the European adult population. This causes a high social and economic burden on European societies. In most of the cases, early diagnosis, can lead to effective treatment, and people who are affected can live a productive life and be integrated in society. Consequently, there is a strong need for an imaging tool that facilitates the diagnosis of schizophrenia early during development. The purpose of this study is to present the results and development of the European FP7-Health-2013: TRIMAGE project, which aims at building an original PET/MR/EEG imaging system for early diagnosis of brain disorders. The 1.5T brain-dedicated MRI scanner is already under operational testing procedures. For comparison reasons, a clinical trial was carried out in 25 subjects (13 healthy control and 12 schizophrenic patients) using an existing clinical MRI scanner. The PET system, with FOV=16.2cm and PET ring diameter of 24cm, is under the final stage of construction, while Monte Carlo simulations, using anthropomorphic computational models, were carried out in order to evaluate the PET system. Finally, the PET/MRI system will be a complete trimodal system since it will incorporate a commercially available state-of-the-art EEG system (32 channels) that has already been tested in the hybrid PET/MRI environment. The proposed system will be fully operational by the end of the project in December 2018.
This work describes the preparation, characterization and functionalization with magnetic nanoparticles of a bone tissue-mimetic scaffold composed of collagen and hydroxyapatite obtained through a ...biomineralization process. Bone remodeling takes place over several weeks and the possibility to follow it
in vivo
in a quick and reliable way is still an outstanding issue. Therefore, this work aims to produce an implantable material that can be followed
in vivo
during bone regeneration by using the existing non-invasive imaging techniques (MRI). To this aim, suitably designed biocompatible SPIONs were linked to the hybrid scaffold using two different strategies, one involving naked SPIONs (nMNPs) and the other using coated and activated SPIONs (MNPs) exposing carboxylic acid functions allowing a covalent attachment between MNPs and collagen molecules. Physico-chemical characterization was carried out to investigate the morphology, crystallinity and stability of the functionalized materials followed by MRI analyses and evaluation of a radiotracer uptake (
99m
TcTc-MDP). Cell proliferation assays
in vitro
were carried out to check the cytotoxicity and demonstrated no side effects due to the SPIONs. The achieved results demonstrated that the naked and coated SPIONs are more homogeneously distributed in the scaffold when incorporated during the synthesis process. This work demonstrated a suitable approach to develop a biomaterial for bone regeneration that allows the monitoring of the healing progress even for long-term follow-up studies.
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