Xinlu Wang's team at the Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, published a study in EJNMMI Research, reporting for the first time the preclinical evaluation and first human imaging of the novel 18F-tagged fibroblast activation protein (FAP)-targeting peptide [18F] AlF-FAP-NUR, and the MadicLab PSA071 PET/CT system in an animal model The MadicLab PSA071 PET/CT system demonstrates high-resolution tumor visualization capabilities in an animal model, providing a new tool for precision cancer diagnosis and treatment.Research Background and Technical ChallengesFAP is specifically highly expressed in tumor-associated fibroblasts (CAFs) and is an ideal target for tumor imaging. Although 68Ga-labeled FAP peptides (e.g., FAP-2286) have been used for PET imaging, the lack of supply of 68Ge/68Ga generators and the short half-life of the nuclide (68 min) have made it difficult to meet the clinical demand for high throughput.18F-labeled probes (half-life of 109.8 min), which can be mass-produced by the medical cyclotron and have a higher spatial resolution, have become an ideal alternative. The 18F labeled probe (half-life 109.8 min) can be mass-produced by medical cyclotron and has higher spatial resolution, making it an ideal alternative.Figure 1: Chemical structures of [68Ga]Ga-FAP-2286, [18F]AlF-FAP-2286 and [18F]AlF-FAP-NURThe central role of MadicLab PET/CT1. Preclinical Animal Imaging: High Resolution Tumor Specific Uptake Assessment Device ParametersUsing MadicLab PSA071 PET/CT with spatial resolution up to 200 μm supports dynamic PET scanning in mouse models.Key Findings In 293T-FAP loaded mice, tumor uptake of [18F]AlF-FAP-NUR (26.99% ID/g) was 2.3 times higher than that of 68Ga-FAP-2286 (11.55% ID/g), with tumor-muscle ratios up to 61.31 vs. 22.66, demonstrating a higher tumor-to-background contrast ratio6-77.Dynamic imaging showed rapid clearance of the probe in the kidney (~50% clearance at 45 min) and low uptake in non-target organs such as muscle (0.35±0.13% ID/g at 60 min), confirming its favorable pharmacokinetic properties.2. Molecular mechanism validation: cellular level uptake and metabolism analysisCELLULAR ASSAYS: Quantitative analysis by MadicLab PET/CT showed that [18F]AlF-FAP-NUR had a significantly higher uptake rate in HT1080-FAP cells (65.77% ID/million cells) than 68Ga-FAP-2286 (42.47%) and a much lower rate of exocytosis (120-minute residue 52%).Metabolic Stability: In vitro stability assays demonstrated that the probe had 90% radiochemical purity in serum at 37°C for 4 hours, supporting clinical translation.Figure 2: In vitro stability and in vitro experimental results of [68Ga]Ga-FAP-2286 and [18F]AlF-FAP-NUR. (A) In vitro stability of [18F]AlF-FAP-NUR at 0.5, 1, 2, and 4 hours. (B) Binding affinity of DOTA-FAP-2286 and NOTA-FAP-NUR in 293T-FAP cells. (C) Uptake of HT1080-FAP cells and HT1080 cells in the presence or absence of DOTA-FAP-2286 as a competitor after 60 min of incubation. (D) Uptake of HT1080-FAP cells after 5-120 min of incubation. (E) Internalization of HT1080-FAP cells after 5-120 min of incubation. (F) Exocytosis kinetics of HT1080-FAP cells incubated with radiolabeled compounds for 60 min followed by 5-120 min of incubation with compound-free medium. Binding affinity data are expressed as mean ± standard deviation (n=3 per group) and other data are n=4 per group. ****P0.0001Figure 3: Figure 4 Micro-PET images and time-activity curves of [68Ga]Ga-FAP-2286 and [18F]AlF-FAP-NUR in male tumor-bearing mice. (A,C) Uptake of [68Ga]Ga-FAP-2286 and [18F]AlF-FAP-NUR was assessed at 60 min in 293T-FAP and 293T loaded tumor-bearing mice (n=4 per group). (B, D) Uptake of [68Ga]Ga-FAP-2286 and [18F]AlF-FAP-NUR at 60 min was assessed in 293T-FAP and 293T homozygous tumor-bearing mice (n=4 per group).Time-activity curves in A-D show the accumulation of radiotracer in the different organs from 5-120 min after injection. (E) Tumor background ratio (TBR) of the two tracers in different xenografts (including 293T-FAP and 293T hormonal mice) at 60 min. (F) TBR of both tracers in different xenografts (including A549-FAP and A549-loaded tumor-bearing mice) at 60 min. All data are expressed as mean % ID/g ± standard deviation (n=4).3. Clinical Translation: First Human PET/CT Imaging Clinical Equipment: Human imaging was performed using the UMI Panorama system, but pre-existing animal model data provided a key reference for clinical dose optimization.Patient results: PET/CT of 2 cancer patients (breast cancer, lung cancer) showed primary tumor SUVmax of 21.20 and 14.19, muscle SUVmean of only 0.65-1.32, and TBR of 10.75-32.62, which verified the tumor-targeting ability of the probes in humans.Figure 4 Clinical images of [18F]AlF-FAP-NUR PET/CT, HE staining results and FAP immunohistochemical staining of the patient's primary focus. (A) Patient with ductal carcinoma of the right breast. (B) Patient with invasive adenocarcinoma of the right lung. Scale bar, 50 μm.Study Conclusions and Future Prospects[18F]AlF-FAP-NUR combined with MadicLab high-resolution PET/CT demonstrated higher tumor-specific uptake and TBR values in animal models, and human imaging preliminarily confirmed its safety and efficacy. Although expanded clinical cohort validation is needed, this technology provides a new paradigm for early diagnosis and efficacy monitoring of FAP-positive tumors. In the future, it can be combined with the dynamic imaging capability of the MadicLab device to further optimize the pharmacokinetics of the probe and promote the development of precision nuclear medicine therapy.Link to paper: DOI: 10.1186/s13550-024-01139-wEquipment Support: MadicLab PSA071 PET/CT System (Shandong Madec Yinghua Technology Co., Ltd.)

Prof. Zhigang Liu's team from the School of Food Science and Engineering, North West Agriculture and Forestry University (NWAFU) published a study in the international journal iMeta, revealing for the first time the molecular mechanism by which time-restricted feeding (TRF) improves the cognitive function of Alzheimer's disease (AD) by regulating the intestinal flora - propionic acid - free fatty acid receptor 3 (FFAR3) axis and verifying the key processes of metabolites across the blood-brain barrier by using the MagicLab PET/CT technology, providing a new direction for non-pharmacological intervention in AD. With the help of MadicLab PET/CT, the key process of metabolites crossing the blood-brain barrier was verified, which provides a new direction for non-pharmacological intervention in AD.MadicLab PET/CT's Central Role in ResearchIn exploring the neuroprotective mechanism of propionic acid (PA) against AD, the research team utilized the MadicLab Box 071 system to perform positron emission tomography (PET) imaging to validate the distribution and metabolic properties of PA in the brain:• Validation of PA brain penetration: By intravenously injecting [18F]-labeled fluoropropionic acid ([18F]-FPA), PET images showed that PA could penetrate the blood-brain barrier and was significantly enriched in the hippocampus, cortex, striatum and other AD-related brain regions.• Quantification of metabolic dynamics: PET data showed that PA metabolic signals in the brains of AD mice were significantly lower than those of healthy mice, and exogenous PA supplementation restored the metabolic activity of these regions, suggesting that there is a PA metabolic disorder in AD, and that supplementation of PA can reverse this abnormality.• Validation of mechanism relevance: Combined with the FFAR3 knockdown assay, PET imaging confirmed that the neuroprotective effect of PA is dependent on FFAR3 receptor activation, providing direct imaging evidence for the “gut flora metabolite-brain axis” mechanism.Research context and core scientific questionsThe global prevalence of Alzheimer's disease (AD) continues to rise, and the association between intestinal flora disorders and AD pathology has been widely recognized, but how TRF, a non-invasive dietary intervention, exerts neuroprotective effects through the gut-brain axis is not clear. In this study, we aimed to analyze whether the ameliorative effect of TRF on AD is dependent on the intestinal flora and its metabolites, and to explore the key regulatory pathways.Key Methods and Breakthrough Findings 1. Clinical Intervention: TRF Significantly Improves Cognitive Function in AD PatientsDesign: Nine patients with AD underwent a 4-month time-restricted feeding intervention (8-hour daily feeding window), and cognitive changes were assessed using the Montreal Cognitive Assessment Scale (MoCA).• Results: The overall cognitive scores of the patients were significantly improved (p0.05), and the improvement in executive function was particularly significant; the level of fecal propionic acid (PA) was positively correlated with the cognitive scores (r=0.5677, p0.0001), suggesting that PA may be a key metabolic marker for the efficacy of TRF.2. Animal model: TRF alleviates AD pathology through intestinal flora.5xFAD transgenic mouse model: 3-month TRF intervention significantly shortened the latency to escape from Morris water maze, reduced amyloid (Aβ) deposition in the brain by up to 30%, promoted microglia aggregation to Aβ plaques, and reduced the expression of inflammatory factors TNF-α and IL-1β.• Flora clearance assay: After antibiotics cleared the intestinal flora, the cognitive improvement effect of TRF completely disappeared, confirming its dependence on the intestinal flora to mediate it. Supplementation with Bifidobacterium longum (B. pseudolongum) mimicked the effects of TRF, significantly reducing Aβ deposition and elevating PA levels. 3.3. Multi-omics analysis: the central role of the B. pseudolongum-PA-FFAR3 pathwayMicrobiome and metabolome analysis: TRF significantly enriched B. pseudolongum, and its abundance was positively correlated with PA level (r=0.68); PA entered the brain through the blood-brain barrier, activated the FFAR3 receptor, inhibited the phosphorylation of JNK, and up-regulated the neurotrophic factor BDNF.• Molecular mechanism: In FFAR3 knockout mice, the neuroprotective effect of TRF completely disappeared, confirming that FFAR3 is a key target of TRF-PA pathway.Figure : Propionic acid (PA) supplementation improves cognitive deficits in AD mice. (A) Schematic representation of groups treated with PA or carrier (n=7-8). (B) Escape latency. (C) Time spent in the target quadrant. (D) Immunohistochemical fluorescence images of Aβ deposition (green) and Iba-1+ (red) microglia in mouse cortex (n=3) (scale bar, 100 μm)Fig. (E) Quantitative analysis of plaque-positive area. (F) Quantitative analysis of Aβ plaque-associated microglia. (G) mRNA levels of TNF-α (n=6). (H) mRNA levels of IL-1β (n=6). (I) Representative axial, sagittal and coronal positron emission tomography (PET) images showing PA brain uptake. (J) Brain uptake levels of [18F]-FPA (% ID/g) (n=3). (K) Quantitative PET analysis of [18F]-FPA in hippocampus, cortex and striatum. (L) Protein blot analysis of p-JNK and JNK (n=3). Data are expressed as mean ± standard error. *p0.05, **p0.01; two-way ANOVA and Tukey's multiple comparison test were used.Translational potential and clinical significancenormKey effects of the TRF interventionintestinal floraEnrichment of beneficial bacteria such as B. pseudolongum and remodeling of flora structure.metaboliteElevates fecal propionic acid (PA) levels, which positively correlates with cognitive scores and crosses the blood-brain barrier to modulate neuroinflammation.neuropathologyReduces Aβ deposition, inhibits microglia overactivation, and upregulates BDNF to improve neuronal survival.Advantages of non-pharmacological interventionsCompared to traditional drugs, TRF is non-invasive, easy to comply with, and can achieve multi-targeted interventions by modulating the flora-metabolism axis.Potential applicationsProbiotic therapy: B. pseudolongum may be a candidate for AD prevention or adjuvant therapy, and its PA-producing ability is a key characteristic.Metabolite monitoring: Fecal PA level can be used as a non-invasive biomarker for early diagnosis of AD and evaluation of TRF efficacy, and the combination of brain imaging technology with MadicLab PET/CT can further enhance the accuracy of mechanism research.-Combined intervention strategy: Combining TRF and FFAR3 agonists may enhance the neuroprotective effect and provide new ideas for personalized treatment of AD.Challenges and future prospectsCurrent limitations: The clinical sample size is relatively small, and it is necessary to expand the cohort to verify the generalization of PA as a biomarker; the potential effect of long-term TRF on intestinal flora still needs to be observed.Research directions: exploring the optimal intervention dose for B. pseudolongum, optimizing the brain-targeted delivery efficiency of PA analogues using MadicLab PET/CT, and validating the applicability of TRF in other neurodegenerative diseases.Link to paper: DOI:10.1002/imt2.70006Equipment support: MadicLab Box 071 system (Shandong Madec Yinghua Technology Co., Ltd.)

In Linyi, a land full of innovation and vitality, an enterprise named “Shandong Maide Yinghua” is rewriting the competitive pattern of the global nuclear medical imaging field in the name of “Made in China”. From the breakthrough of 0.5mm spatial resolution, to the successful delivery of the international market, this enterprise was established only more than ten years ago, with independent research and development of hard-core technology, for China's high-end medical equipment labeled “world-leading”. Recently, the reporter went into Maide Yinghua, dialogue with the founder Dr. Liu Jiguo, to explore the innovation code and industrial ambition behind this “invisible champion”.Starting from “0” The Icebreaker for Made in ChinaWhat is PET? Simply put, PET reconstructs three-dimensional images (of cancer cells) through positron emission, and is a powerful tool for clinical cancer screening.After graduating from the Department of Modern Physics at CUHK with a Ph.D. in 2004, Liu Jiguo went to MD Anderson Cancer Research Center in the U.S. to work on PET equipment research and development. “PET (Positron Emission Tomography) is known as the ‘jewel in the crown of medical imaging’ and is the gold standard for cancer diagnosis, but at that time there was almost a blank in this field in China.”During his stay in the U.S., he deeply felt the constraints imposed by the technology monopoly. "PET equipment can easily be ten million price, the core technology has long been monopolized by European and American companies. Chinese patients can not afford to use, hospitals can not afford to buy, this passive situation stung me." In 2007, he decided to return to China, determined to promote the localization of PET.However, the road to entrepreneurship is far more difficult than imagined. "In 2012, we were introduced by the city of Linyi as the first high-level science and technology entrepreneurial team, and established Maide Yinghua. 'Maide Yinghua' is taken from the homonym of ‘Made in China’, which is to proclaim to the world: made in China, it is just as capable of scaling the technological peak."He admits that it took great courage to choose the name “Made in China”. "At that time, some people advised us to emphasize the domestic identity, the market may not buy. But we had to go against the trend - only by facing up to the challenges can we force ourselves to make a breakthrough."As he puts it, the early days of the business were like “climbing uphill from a pit”: the first device was sold for millions of dollars, and customers had very little trust in homegrown technology. 2015, the first order from the First Hospital Affiliated to China Medical University became a key turning point in the survival of the enterprise. “That device was our ‘lifeline’, and every part and every line of code coalesced with the team's desperate efforts.”The Ultimate Challenge of 0.42mm The Ten-Year Climb of Core Technology Autonomy“0.5mm was once the industry's recognized physical limit.” Liu Jiguo tells a story of conviction and detail: in 2010, when the team proposed a goal of “0.5-millimeter resolution,” skepticism was rampant. "Mouse imaging needs to achieve 1/10 of the resolution of human devices, i.e., 0.5 millimeters. But at that time, the highest international level was only 0.7 millimeters, which many peers considered an ‘impossible task’."The team opted for a step-by-step breakthrough: realizing 0.6 mm in 2019, conquering 0.5 mm in 2020, and eventually raising the resolution to 0.42 mm. "Behind this are hundreds of process innovations. For example, crystal processing precision has been increased from the industry-universal 10 microns to 3 microns, which alone jumped detector performance by 30%." He concludes, “Disruptive innovation is not a breakthrough at a single point, but the extreme polishing of the whole chain. 5% optimization of each of the 10 links can increase the overall performance by 50%.”Nowadays, the resolution of PET equipment of MET is the first in the world, and the related technology has been included in the “14th Five-Year Plan” textbook “Nuclear Medicine” of national medical schools. Liu Jiguo exclaimed: "It took us ten years from following to leading. This proves that Made in China can not only ‘live’, but also define new standards in the industry."The Golden Age of Nuclear Medicine Ecological Layout of a Trillion-Dollar Market“Nuclear medicine physics is ushering in the era of ‘tripod’.” Liu Jiguo analysis, imaging diagnostics, radiation therapy, nuclide-targeted drugs three major directions constitute a trillion-dollar market. Among them, the imaging equipment market size of more than 300 billion yuan, and nuclide drugs in recent years, the growth rate of up to 40%. “The policy dividend is also ramping up - in 2021, the state released the Medium and Long-term Development Plan for Medical Isotopes, which explicitly supports the development of the nuclear technology application industry.”In the face of opportunities, McDonald's chooses to “focus on imaging, ecological synergy”. “We will continue to deepen our efforts in PET, SPECT, and CT multimodal imaging equipment, and at the same time, we will unite upstream and downstream to build a ‘Linyi nuclear medicine ecosystem’.” He revealed that the company has organized the “Linyi Nuclear Medicine Molecular Imaging Conference” for ten consecutive years, attracting dozens of academicians and thousands of experts. “Our goal is to make Linyi a nuclear medicine innovation highland, so that academic exchanges can be transformed into industrial landing.”In the internationalization layout, the enterprise also has a firm pace. 2023, the first PET equipment exported to the U.S. completed loading, and the second one will be delivered soon. "In the next three years, the proportion of overseas orders is planned to increase from 10% to 50%. Chinese technology should not only serve the local community, but also participate in global competition."Beyond Business Social responsibility and corporate culture run in both directions“Businesses can't survive without making a profit, but the real value lies in pushing the industry forward.” Liu Jiguo shared a predecessor's admonition: “Only when China's nuclear medicine is good, can the enterprise be good.” To this end, Meade has always practiced the concept of “technology for all” - breaking through the resolution limit through independent research and development, making the image clarity jump to a new height in the industry, and helping grassroots hospitals to build a precise diagnosis and treatment system.Social responsibility is also reflected in the cultivation of talents. “Linyi used to be a ‘talent depression’, but we firmly believe that ‘first-class talents determine first-class products’.” The company has established a culture of “extreme challenges”: encouraging the team to overcome “impossible goals” and improving the ability of employees through internal training. "Ten years ago, when we proposed the 0.5mm target, even the industry leaders thought it was crazy. But it was this ‘dare to think, dare to do’ boldness that transformed the mediocre team into the top team."The next ten years defines the new height of “China's creativity”.Standing at a new starting point, Liu Jiguo has drawn a clear blueprint for the future of METC: in the field of technology depth, research and development of the next generation of ultra-high definition PET-CT, and exploration of artificial intelligence-assisted diagnostic systems; in the field of industrial synergy, the development of nuclide-targeted drugs in cooperation with pharmaceutical companies, and to open up the closed loop of “diagnosis - treatment”; In terms of industrial synergy, we will cooperate with pharmaceutical companies to develop nuclear-targeted drugs and open up the closed loop of “diagnosis and treatment”; and in terms of global layout, we will expand the market in Europe and America and realize "localized innovation + globalized application.“In the past ten years, we have proved the tenacity of China's manufacturing; in the next ten years, we want to make ‘China's creation’ become the benchmark of global nuclear medicine.” At the end of the interview, Liu Jiguo's gaze is firm and fiery.From the old area of Yimeng to the world stage, the story of Maide Yinghua is not only an epic of the growth of an enterprise, but also a song of China's high-end manufacturing breakthrough. Here, the precision of 0.42 millimeters measures the depth of technology, and also marks the temperature of industry serving the country.When “Made in China” tore off the old labels and reshaped the global competition pattern with innovation and commitment, the journey of Madec Yinghua is the best footnote of this era.