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PaperOptimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile
Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profileBackgroundIron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments.ResultsThe optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM− 1s− 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg.ConclusionsThis study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.Journal of Nanobiotechnology volume 22, Article number: 419 (2024)Link: Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile | Journal of Nanobiotechnology | Full Text (biomedcentral.com)
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PaperClinical Performance Evaluation of an Artificial Intelligence-Powered Amyloid Brain PET Quantification Method
Clinical Performance Evaluation of an Artificial Intelligence-Powered Amyloid Brain PET Quantification MethodPurposeThis study assesses the clinical performance of BTXBrain-Amyloid, an artificial intelligence-powered software for quantifying amyloid uptake in brain PET images.Methods150 amyloid brain PET images were visually assessed by experts and categorized as negative and positive. Standardized uptake value ratio (SUVR) was calculated with cerebellum grey matter as the reference region, and receiver operating characteristic (ROC) and precision-recall (PR) analysis for BTXBrain-Amyloid were conducted. For comparison, same image processing and analysis was performed using Statistical Parametric Mapping (SPM) program. In addition, to evaluate the spatial normalization (SN) performance, mutual information (MI) between MRI template and spatially normalized PET images was calculated and SPM group analysis was conducted.ResultsBoth BTXBrain and SPM methods discriminated between negative and positive groups. However, BTXBrain exhibited lower SUVR standard deviation (0.06 and 0.21 for negative and positive, respectively) than SPM method (0.11 and 0.25). In ROC analysis, BTXBrain had an AUC of 0.979, compared to 0.959 for SPM, while PR curves showed an AUC of 0.983 for BTXBrain and 0.949 for SPM. At the optimal cut-off, the sensitivity and specificity were 0.983 and 0.921 for BTXBrain and 0.917 and 0.921 for SPM12, respectively. MI evaluation also favored BTXBrain (0.848 vs. 0.823), indicating improved SN. In SPM group analysis, BTXBrain exhibited higher sensitivity in detecting basal ganglia differences between negative and positive groups.ConclusionBTXBrain-Amyloid outperformed SPM in clinical performance evaluation, also demonstrating superior SN and improved detection of deep brain differences. These results suggest the potential of BTXBrain-Amyloid as a valuable tool for clinical amyloid PET image evaluation.Keywords: Amyloid, Alzheimer dementia, Spatial normalization, Deep learning, QuantificationNucl Med Mol Imaging. 2024 Jun; 58(4): 246–254. doi: 10.1007/s13139-024-00861-6Link: Clinical Performance Evaluation of an Artificial Intelligence-Powered Amyloid Brain PET Quantification Method - PMC (nih.gov)
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NewsBrightonix Imaging Obtains Medical Device Manufacturing Certification for Korea's First Developed Clinical PET System
Brightonix Imaging Obtains Medical Device Manufacturing Certification for Korea's First Developed Clinical PET System▲ PHAROS 'PHAROS', the first clinical positron emission tomography (PET) system developed by deep-tech startup Brightonix Imaging (Jae Sung Lee, CEO) in Korea, received a medical device manufacturing certificate from the Korea's National Institute of Medical Device Safety Information on February 13th.'PHAROS' is a versatile and multifunctional digital PET system that allows brain imaging in the sitting or supine position and breast imaging in the prone position. It can be installed and operated in a smaller space compared to conventional whole-body PET/CT. Brain PET scans are expected to play a major role in the early detection and treatment of brain diseases, especially as the incidence of degenerative brain diseases is increasing due to the aging population, and the U.S. FDA's accelerated approval of Biogen's Leqembi and Eli Lilly's successful Phase III clinical trial of Donanemab. 'PHAROS' has been developed with close support from Korea Medical Device Development Fund, where streamlined the entire process from product development to regulatory approval. Recognized for its forward-looking feaures and high potential for future advancements in the medical device field, it has garnered significant attention from both the market and the industry, earning recognition as one of the top 10 representative achievements by the KMDF team. Brightonix Imaging's CEO, Jae Sung Lee, expressed significant meaning in obtaining the medical device manufacturing certification for the 'PHAROS' system. He emphasized that this achievement, marking the first domestically produced clinical PET system to receive medical device manufacturing certification, is the result of the dedicated efforts of many researchers working towards the localization of PET systems, along with continuous support from the government. Lee stated, "This milestone holds great significance, as it signifies the culmination of valuable efforts. Moving forward, we aim not only to penetrate the domestic market but also to showcase the excellence of domestically produced medical devices on the global stage through FDA/CE certifications." In addition, Dr. Guen Bae Ko, CTO of Brightonix Imaging explained, "'PHAROS' has achieved a revolutionary improvement in the spatial resolution uniformity of PET images by precisely measuring gamma-ray reaction depth information within the scintillation crystal, a feature not provided by conventional whole-body PET/CT systems. With a specialized design for local organs such as the brain, it will minimize patient radiation exposure, enabling more efficient and accurate diagnoses."<저작권자 ⓒ 약품신문 무단전재 및 재배포 금지>출처: 브라이토닉스이미징, 국내 최초 개발 임상용 PET 시스템 의료기기 제조인증 획득:약품신문 - https://www.yakpum.co.kr/12853
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PaperCerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouse
Cerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouseRationale: [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity. However, it is challenging to obtain iBAT-specific images using [18F]FDG-PET because increased uptake of [18F]FDG is observed in tumors, muscle, and inflamed tissues. Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker. Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation. In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging. However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse. Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly. Therefore, we selected [18F]fm-PBR28-d2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse.Methods: UCP1 ThermoMouse was used to monitor UCP1 expression. Western blotting and immunohistochemistry were performed to measure the level of protein expression. [18F]fm-PBR28-d2 and [18F]FDG were used as radioactive probes for iBAT imaging. PET images were acquired with SimPET, and optical images were acquired with IVIS 100.Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT. In both PET and CLI, the TSPO-targeting probe [18F]fm-PBR28-d2 was superior to [18F]FDG for acquiring iBAT images. The high molar activity of the probe was essential for CLI and PET imaging. We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI. Both signals of iBAT were clearly increased after cold stimulation. Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups.Conclusion: We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [18F]FDG-PET/CLI under the various conditions. Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.Keywords: Interscapular brown adipose tissue, UCP1, TSPO, PET, Cerenkov luminescence imagingLink: Cerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouse - PMC (nih.gov)
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NewsDr. Jae Sung Lee, CEO of Brightonix Imaging delivers a Plenary Talk at IEEE NSS/MIC/RTSD
Dr. Jae Sung Lee, CEO of Brightonix Imaging delivers a Plenary Talk at IEEE NSS/MIC/RTSDAdvancements in digital PET and artificial intelligence and promising technologies for the futureBrightonix Imaging, a medical imaging company, announced that Dr. Jae Sung Lee, CEO of Brightonix Imaging and Professor of Nuclear Medicine at Seoul National University, delivered a plenary talk at the Institute of Electrical and Electronics Engineers' Nuclear Science, Medical Imaging, and Room Temperature Semiconductor Detector Conference (IEEE NSS/MIC/RTSD) in Vancouver, Canada last week. At the plenary session held on the 6th of this month, Lee delivered a lecture on the development history and recent trends of digital positron emission tomography (PET) and artificial intelligence technologies that have revolutionised the field of nuclear medicine molecular imaging, highlighting the significant impact of technological innovation on the development of medical imaging and introducing promising technologies for the future.After receiving the Medical Imaging Technical Achievement Award from the IEEE's Nuclear and Plasma Society (NPSS) last year, which recognises a researcher who has made innovative contributions to the field of medical imaging technology based on their cumulative research achievements and leadership, Lee was invited to deliver the keynote lecture at this year's conference, the largest conference organised by the NPSS. Lee was also invited to speak at the 'Ultra-Low Dose PET Workshop' on the 11th, the last day of the conference, where he introduced the latest artificial intelligence technology for ultra-low dose PET and the core technology of the Pharos system, a high-resolution, multi-purpose PET developed with the support of the Korea Medical Device Development Fund, and is planning a clinical evaluation at Seoul National University Hospital.<Copyright ⓒ 약품신문 무단전재 및 재배포 금지>출처: 브라이토닉스이미징 이재성 대표, 국제전기전자공학회‘기조연설-약품신문 - http://www.yakpum.co.kr/10294
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NewsBrightonix Imaging receives Excellence Award on Pitching & Connect Day held by Seoul Start-up Hub Scale-up Center
Brightonix Imaging receives Excellence Award on Pitching & Connect Day held by Seoul Start-up Hub Scale-up Center Brightonix Imaging Inc. (led by Jae Sung Lee, CEO), a deep-tech medical imaging specialist, was awarded the Excellence Award at the Seoul Startup Hub Scale-up Pitching & Connect Day event organized by the Seoul Business Agency (SBA) and Hana Ventures. The event took place on July 6th at the eoul Startup Hub Scale-up Center, located in the Korea Science and Technology Center in Gangnam-gu, Seoul. Among the 140 companies that Hana Ventures has invested in over the past five years, eight outstanding portfolio companies were pre-selected through screening to participate in the IR pitching session. Among them, four outstanding companies were selected and awarded. Brightonix Imaging was recognized for commercializing positron emission tomography (PET) for the first time in Korea, starting with the supply to the U.S. National Institutes of Health (NIH) and generating overseas exports, and for the excellent performance of the Pharos PET system, which is being developed to respond to the demand for PET testing for Alzheimer's disease, which is expected to increase rapidly in the future.In addition, BTXBrain, an artificial intelligence (AI)-based brain PET/SPECT image analysis software that secured an unparalleled sales advantage within six months of domestic medical device approval, was also recognized for supplying it to leading medical institutions such as Seoul National University Hospital and Seoul St. Mary's Hospital in collaboration with GE and Siemens. "By next year, we will complete the licensing of the Pharos PET system and BTXBrain medical devices in Korea, the U.S., and Europe," said Jae Sung Lee, CEO of Brightonix Imaging. "Brightonix Imaging will show that Korea's advanced medical device technology can work in the ultra-high-end medical imaging market." <저작권자 ⓒ 약품신문 무단전재 및 재배포 금지>출처: 브라이토닉스이미징, 서울창업허브 스케일업 피칭&커넥트데이 우수상 수상-약품신문 - http://www.yakpum.co.kr/6703