{"title":"The different manifestations of <sup>18</sup>F-FDG PET/CT and <sup>68</sup>Ga-FAPI-04 PET/CT in evaluation of the steroid therapy response for IgG4-related disease: A case report.","authors":"Guorong Jia, Dejian Bian, Chao Cheng, Meitang Wang, Changjing Zuo","doi":"10.3389/fnume.2022.1038797","DOIUrl":"10.3389/fnume.2022.1038797","url":null,"abstract":"<p><p>IgG4-related disease is a fibrous-inflammatory process belonging to immunomodulation disorders. We report a case of a 57-year-old man with the IgG4-related disease (RD). <sup>68</sup>Ga-FAPI-04 PET/CT showed more significant uptake in most lesions than in <sup>18</sup>F-FDG PET/CT except for the cervical and mediastinal lymph nodes. Besides, uptake in the submandibular glands were only detected in <sup>68</sup>Ga-FAPI-04 PET/CT. The biopsy result of the cervical lymph nodes confirmed the diagnosis of IgG4-related disease. After treatment, only slight FDG-avid cervical lymph nodes were observed in the <sup>18</sup>F-FDG PET/CT, while the raised uptake of <sup>68</sup>Ga-FAPI-04 could be observed in the pancreas and submandibular glands. <sup>68</sup>Ga-FAPI-04 PET-CT might have promising applications in evaluating IgG4-RD, whether in initial or follow-up imaging during steroid therapy.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"2 1","pages":"1038797"},"PeriodicalIF":0.0,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42074887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vinay Banka, Andrew Kelleher, Dag Sehlin, Greta Hultqvist, Einar M Sigurdsson, Stina Syvänen, Yu-Shin Ding
{"title":"Development of brain-penetrable antibody radioligands for <i>in vivo</i> PET imaging of amyloid-β and tau.","authors":"Vinay Banka, Andrew Kelleher, Dag Sehlin, Greta Hultqvist, Einar M Sigurdsson, Stina Syvänen, Yu-Shin Ding","doi":"10.3389/fnume.2023.1173693","DOIUrl":"https://doi.org/10.3389/fnume.2023.1173693","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aβ) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood-brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aβ aggregates via <i>ex vivo</i> imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled specifically engineered bispecific antibody probes for the selective detection of tau and Aβ aggregates to evaluate their feasibility and specificity, particularly for <i>in vivo</i> PET imaging.</p><p><strong>Methods: </strong>We first created and evaluated (via both <i>in vitro</i> and <i>ex vivo</i> studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aβ or tau or with their respective scFv. Using [<sup>18</sup>F]SFB as the prosthetic group, all four <sup>18</sup>F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [<sup>18</sup>F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ~ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size exclusion gravity column.</p><p><strong>Results: </strong>Based on both <i>in vitro</i> and <i>ex vivo</i> evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [<sup>18</sup>F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [<sup>18</sup>F]SFB and bispecific antibodies showed a 65%-83% conversion efficiency with radiochemical purities of 95%-99% by radio-TLC.</p><p><strong>Conclusions: </strong>We successfully labeled four novel and specifically engineered bispecific antibodies with [<sup>18</sup>F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aβ aggregates in the brain of transgenic AD mice via <i>in vivo</i> PET imaging.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10483511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10577731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R S L Lima, A Bezerra, M Andrade, C Domenico, A De Lorenzo
{"title":"Improved detection of coronary artery disease by CZT regional coronary blood flow evaluation.","authors":"R S L Lima, A Bezerra, M Andrade, C Domenico, A De Lorenzo","doi":"10.3389/fnume.2022.1072729","DOIUrl":"10.3389/fnume.2022.1072729","url":null,"abstract":"<p><strong>Introduction: </strong>CZT cameras have enabled the noninvasive quantification of myocardial flow reserve (MFR), an important physiologic measure. This study aimed to compare myocardial perfusion SPECT (MPS) with or without MFR evaluation for the detection of obstructive coronary artery disease (CAD).</p><p><strong>Methods: </strong>48 patients with CAD (>50% obstruction) detected at invasive coronary angiography or CT angiography underwent dipyridamole MPS and MFR evaluation within 30 days. A 1-day protocol (rest-stress) was used to quantify MFR. The acquisition of dynamic rest and stress images was initiated simultaneously to 99mTc sestamibi injection (370 and 1,110 MBq, respectively), both lasting for 11 min, followed by 5-min imaging. Pharmacologic stress with dipyridamole (0.56 mg/kg for 4 min) was performed with the patient positioned in the CZT camera. The images were processed and time-activity curves were generated, calculating global and regional MFR in a semiautomatic software. A global or regional MFR <2 was considered abnormal. MPS perfusion images were classified as normal or abnormal. The images were interpreted by experienced physicians blinded to the results of MFR and coronary angiography/CT.</p><p><strong>Results: </strong>Mean age of the population was 61 ± 9 years, 54.2% female. Twenty patients (41.7%) had single-vessel CAD, 22 (45.8%) 2-vessel CAD and 6 (12.5%), triple-vessel CAD. Among the 82 vessels with obstruction, 48 had perfusion abnormalities in MPS and 60 had reduced MFR, while among the normal vessels, had 54 normal MPS and 52 had preserved MFR. The sensitivity of MFR (69%) was higher than that of MPS (55.2%), without significant changes in specificity (86 vs. 83.7%).</p><p><strong>Conclusions: </strong>MFR in the CZT camera is more sensitive for the detection of CAD than perfusion abnormalities in MPS, especially in patients with multivessel CAD.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"1072729"},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49551718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camila Munoz, Alina Schneider, René M Botnar, Claudia Prieto
{"title":"Recent advances in PET-MRI for cardiac sarcoidosis.","authors":"Camila Munoz, Alina Schneider, René M Botnar, Claudia Prieto","doi":"10.3389/fnume.2022.1032444","DOIUrl":"10.3389/fnume.2022.1032444","url":null,"abstract":"<p><p>The diagnosis of cardiac sarcoidosis (CS) remains challenging. While only a small fraction of patients with systemic sarcoidosis present with clinically symptomatic CS, cardiac involvement has been associated with adverse outcomes, such as ventricular arrhythmia, heart block, heart failure and sudden cardiac death. Despite the clinical relevance of having an early and accurate diagnosis of CS, there is no gold-standard technique available for the assessment of CS. Non-invasive PET and MR imaging have shown promise in the detection of different histopathological features of CS. More recently, the introduction of hybrid PET-MR scanners has enabled the acquisition of these hallmarks in a single scan, demonstrating higher sensitivity and specificity for CS detection and risk stratification than with either imaging modality alone. This article describes recent developments in hybrid PET-MR imaging for improving the diagnosis of CS and discusses areas of future development that could make cardiac PET-MRI the preferred diagnostic tool for the comprehensive assessment of CS.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"1032444"},"PeriodicalIF":0.0,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42232585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Lopes van den Broek, Rocío García-Vázquez, Ida Vang Andersen, Guillermo Valenzuela-Nieto, Vladimir Shalgunov, Umberto M Battisti, David Schwefel, Naphak Modhiran, Vasko Kramer, Yorka Cheuquemilla, Ronald Jara, Constanza Salinas-Varas, Alberto A Amarilla, Daniel Watterson, Alejandro Rojas-Fernandez, Matthias M Herth
{"title":"Development and evaluation of an <sup>18</sup>F-labeled nanobody to target SARS-CoV-2's spike protein.","authors":"Sara Lopes van den Broek, Rocío García-Vázquez, Ida Vang Andersen, Guillermo Valenzuela-Nieto, Vladimir Shalgunov, Umberto M Battisti, David Schwefel, Naphak Modhiran, Vasko Kramer, Yorka Cheuquemilla, Ronald Jara, Constanza Salinas-Varas, Alberto A Amarilla, Daniel Watterson, Alejandro Rojas-Fernandez, Matthias M Herth","doi":"10.3389/fnume.2022.1033697","DOIUrl":"10.3389/fnume.2022.1033697","url":null,"abstract":"<p><p>COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) - a small, engineered protein derived from alpacas - and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to <sup>18</sup>F-label the NB under mild conditions once the NBs were successfully modified with <i>trans-</i>cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate <i>in vivo</i> binding to the Spike protein with our radioligands.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"1033697"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42078734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alice Packham, Niamh Spence, Tanveer Bawa, Rohit Srinivasan, Anna L Goodman
{"title":"The role of [18F]FDG-PET/CT in gram-positive and gram-negative bacteraemia: A systematic review.","authors":"Alice Packham, Niamh Spence, Tanveer Bawa, Rohit Srinivasan, Anna L Goodman","doi":"10.3389/fnume.2022.1066246","DOIUrl":"10.3389/fnume.2022.1066246","url":null,"abstract":"<p><strong>Objectives: </strong>Bacteraemia is associated with significant morbidity and mortality. [18F]FDG-PET/CT is increasingly used to detect infectious metastatic foci, however there remains international variation in its use. We performed a systematic review assessing the impact of [18F]FDG-PET/CT in adult inpatients with gram-positive and Gram-negative bacteraemia.</p><p><strong>Design: </strong>The systematic review was performed according to PRISMA guidelines. Studies published between 2009 and December 2021 were searched in MEDLINE, EMBASE and Cochrane clinical trials database. Data extraction and quality assessment was performed using ROBINS-I and GRADE.</p><p><strong>Setting: </strong>Eligible study designs included randomised-controlled trials, clinically-controlled trials, prospective trials, retrospective trials, case-control studies, and non-controlled studies.</p><p><strong>Participants: </strong>Studies solely assessing adult inpatients with blood-culture confirmed bacteraemia with one cohort of patients receiving [18F]FDG-PET/CT were included.</p><p><strong>Main outcome measures: </strong>primary outcomes were mortality, identification of metastatic foci and relapse rate. Studies not examining any of the pre-specified outcomes were excluded.</p><p><strong>Results: </strong>Ten studies were included, of which five had a non-PET/CT control arm. Overall, there was low quality of evidence that [18F]FDG-PET/CT is associated with reduced mortality, improved identification of metastatic foci and reduced relapse rate. Six studies assessed <i>Staphylococcus aureus</i> bacteraemia (SAB) only; nine studies included Gram-positive bacteraemia only, and one study included data from Gram-negative bacteraemia. Two studies compared outcomes between patients with different types of bacteraemia. Four studies identified a statistically significant difference in mortality in [18F]FDG-PET/CT recipients and controls. Relapse rate was significantly reduced in patients with SAB who received [18F]FDG-PET/CT. Studies identified significantly higher detection of metastatic foci in [18F]FDG-PET/CT recipients compared to controls. [18F]FDG-PET/CT was the first to identify an infectious site in 35.5% to 67.2% of overall foci identified.</p><p><strong>Conclusions: </strong>Further research is required to establish the role of [18F]FDG-PET/CT in bacteraemia, and its impact on management and mortality.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"1066246"},"PeriodicalIF":0.0,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45924682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Broadening the selection criteria for Astronauts undertaking long-term space travel.","authors":"Hiroshi Yasuda, Lembit Sihver","doi":"10.3389/fnume.2022.997718","DOIUrl":"10.3389/fnume.2022.997718","url":null,"abstract":"","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"997718"},"PeriodicalIF":0.0,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42878367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingyu Mu, Xiaoxue Huang, Meng Li, Wenjie Sun, Wei Fu
{"title":"Comparison of physiological uptake of normal tissues in patients with cancer using <sup>18</sup>F-FAPI-04 and <sup>18</sup>F-FAPI-42 PET/CT.","authors":"Xingyu Mu, Xiaoxue Huang, Meng Li, Wenjie Sun, Wei Fu","doi":"10.3389/fnume.2022.927843","DOIUrl":"10.3389/fnume.2022.927843","url":null,"abstract":"<p><strong>Purpose: </strong>To calculate the physiological uptake of various tissues in patients with cancer using <sup>18</sup>F-AlF-NOTA-FAPI-04 (<sup>18</sup>F-FAPI-04) and <sup>18</sup>F-AlF-NOTA-FAPI-42 (<sup>18</sup>F-FAPI-42) PET/CT and to compare the variation in standard uptake values between the two scans.</p><p><strong>Materials and methods: </strong>This retrospective analysis included 40 patients with cancer who underwent <sup>18</sup>F-FAPI; the first 20 patients received <sup>18</sup>F-FAPI-04 PET/CT and the remaining 20 patients received <sup>18</sup>F-FAPI-42 PET/CT. A total of 49 normal tissues, including the brain (cerebrum/cerebellum), parotid and submandibular glands, palatine tonsils, and thyroid, were identified on CT images. For these normal tissues, maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were calculated. We also compared the SUVmean of identical tissues to explore the difference in biodistribution between the two radiotracers.</p><p><strong>Results: </strong>The accumulation of <sup>18</sup>F-FAPI-04 and <sup>18</sup>F-FAPI-42 showed an analogous pattern. High uptake of both radiotracers in the gallbladder, uterus, submandibular gland, and renal pelvis was demonstrated (range: SUVmax, 4.01-5.75; SUVmean, 2.92-4.22). Furthermore, the uptake of bony tissues was slightly higher in <sup>18</sup>F-FAPI-42 than in <sup>18</sup>F-FAPI-04 (range: SUVmean, 0.4 ± 0.22-0.9 ± 0.34 and 0.3 ± 0.24-0.7 ± 0.18, respectively, <i>p</i> < 0.05), while the uptake of some soft tissues was higher in <sup>18</sup>F-FAPI-04 than in <sup>18</sup>F-FAPI-42 (range: SUVmean, 0.9 ± 0.24-1.5 ± 0.35 and 0.9 ± 0.26-1.2 ± 0.37, respectively, <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Both radioligands exhibited similar physiological uptake of normal tissues in patients with cancers. In addition, <sup>18</sup>F-FAPI-42 demonstrated higher uptake of bone tissues than <sup>18</sup>F-FAPI-04 while showing lower uptake of soft tissues than <sup>18</sup>F-FAPI-04.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"927843"},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42388048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Leveraging law and ethics to promote safe and reliable AI/ML in healthcare.","authors":"Katherine Drabiak","doi":"10.3389/fnume.2022.983340","DOIUrl":"10.3389/fnume.2022.983340","url":null,"abstract":"<p><p>Artificial intelligence and machine learning (AI/ML) is poised to disrupt the structure and delivery of healthcare, promising to optimize care clinical care delivery and information management. AI/ML offers potential benefits in healthcare, such as creating novel clinical decision support tools, pattern recognition software, and predictive modeling systems. This raises questions about how AI/ML will impact the physician-patient relationship and the practice of medicine. Effective utilization and reliance on AI/ML also requires that these technologies are safe and reliable. Potential errors could not only pose serious risks to patient safety, but also expose physicians, hospitals, and AI/ML manufacturers to liability. This review describes how the law provides a mechanism to promote safety and reliability of AI/ML systems. On the front end, the Food and Drug Administration (FDA) intends to regulate many AI/ML as medical devices, which corresponds to a set of regulatory requirements prior to product marketing and use. Post-development, a variety of mechanisms in the law provide guardrails for careful deployment into clinical practice that can also incentivize product improvement. This review provides an overview of potential areas of liability arising from AI/ML including malpractice, informed consent, corporate liability, and products liability. Finally, this review summarizes strategies to minimize risk and promote safe and reliable AI/ML.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"983340"},"PeriodicalIF":0.0,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42452464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Lopes van den Broek, Dag Sehlin, Jens V Andersen, Blanca I Aldana, Natalie Beschörner, Maiken Nedergaard, Gitte M Knudsen, Stina Syvänen, Matthias M Herth
{"title":"The Alzheimer's disease 5xFAD mouse model is best suited to investigate pretargeted imaging approaches beyond the blood-brain barrier.","authors":"Sara Lopes van den Broek, Dag Sehlin, Jens V Andersen, Blanca I Aldana, Natalie Beschörner, Maiken Nedergaard, Gitte M Knudsen, Stina Syvänen, Matthias M Herth","doi":"10.3389/fnume.2022.1001722","DOIUrl":"10.3389/fnume.2022.1001722","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common neurodegenerative disease, with an increasing prevalence. Currently, there is no ideal diagnostic molecular imaging agent for diagnosing AD. Antibodies (Abs) have been proposed to close this gap as they can bind selectively and with high affinity to amyloid β (Aβ)-one of the molecular hallmarks of AD. Abs can even be designed to selectively bind Aβ oligomers or isoforms, which are difficult to target with small imaging agents. Conventionally, Abs must be labeled with long-lived radionuclides which typically results in in high radiation burden to healthy tissue. Pretargeted imaging could solve this challenge as it allows for the use of short-lived radionuclides. To develop pretargeted imaging tools that can enter the brain, AD mouse models are useful as they allow testing of the imaging approach in a relevant animal model that could predict its clinical applicability. Several mouse models for AD have been developed with different characteristics. Commonly used models are: 5xFAD, APP/PS1 and tg-ArcSwe transgenic mice. In this study, we aimed to identify which of these models were best suited to investigate pretargeted imaging approaches beyond the blood brain barrier. We evaluated this by pretargeted autoradiography using the Aβ-targeting antibody 3D6 and an <sup>111</sup>In-labeled Tz. Evaluation criteria were target-to-background ratios and accessibility. APP/PS1 mice showed Aβ accumulation in high and low binding brain regions and is as such less suitable for pretargeted purposes. 5xFAD and tg-ArcSwe mice showed similar uptake in high binding regions whereas low uptake in low binding regions and are better suited to evaluate pretargeted imaging approaches. 5xFAD mice are advantaged over tg-ArcSwe mice as pathology can be traced early (6 months compared to 18 months of age) and as 5xFAD mice are commercially available.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":" ","pages":"1001722"},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45633407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}