Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan
{"title":"Preclinical and Clinical-Scale Magnetic Particle Imaging of Natural Killer Cells: in vitro and ex vivo Demonstration of Cellular Sensitivity, Resolution, and Quantification.","authors":"Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan","doi":"10.1007/s11307-024-01969-z","DOIUrl":"10.1007/s11307-024-01969-z","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.</p><p><strong>Procedures: </strong>Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 10<sup>6</sup>) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.</p><p><strong>Results: </strong>NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 10<sup>4</sup> cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 10<sup>7</sup> labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.</p><p><strong>Conclusion: </strong>MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"78-88"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengquan Hu, Jinyan Liu, Haoyu Deng, Na Chen, Lu Chen, Sha Wang, Tingting Long, Jia Tan, Shuo Hu
{"title":"Evaluation of Inflammatory Activity of Extraocular Muscles in Thyroid Associated Orbitopathy by [<sup>68</sup>Ga]DOTATATE PET/CT.","authors":"Zhengquan Hu, Jinyan Liu, Haoyu Deng, Na Chen, Lu Chen, Sha Wang, Tingting Long, Jia Tan, Shuo Hu","doi":"10.1007/s11307-024-01970-6","DOIUrl":"10.1007/s11307-024-01970-6","url":null,"abstract":"<p><strong>Purpose: </strong>The accurate assessment of inflammatory activity of the extraocular muscles (EOMs) in thyroid associated ophthalmopathy (TAO) is crucial for formulating subsequent treatment strategies and prognostic judgments. This study aims to explore the efficacy of using [<sup>68</sup>Ga]DOTATATE PET/CT to assess the inflammatory activity of EOMs in TAO patients.</p><p><strong>Procedures: </strong>This study enrolled 22 TAO patients and 6 healthy volunteers, all of whom underwent orbital [<sup>68</sup>Ga]DOTATATE PET/CT. Among these, 18 patients underwent orbital [<sup>99m</sup>Tc]DTPA SPECT/CT within one week, and the other 4 patients received orbital MRI. All imaging data were independently assessed, followed by comparative data analysis. The patients then received different treatment schemes, and their prognosis was followed up.</p><p><strong>Results: </strong>[<sup>68</sup>Ga]DOTATATE PET/CT could effectively evaluate the inflammatory activity of the EOMs in TAO patients and demonstrate good consistency with [<sup>99m</sup>Tc]DTPA SPECT/CT and orbital MRI, but show a better resolution to distinguish EOMs and surrounding structure. The receiver operating characteristic (ROC) curves for each EOM, treated as individual research units, exhibited an area under the curve (AUC) exceeding 0.9. The medial rectus demonstrated the highest involvement and diagnostic accuracy(AUC = 0.976, P < 0.001). Patients treated with glucocorticoids showed significantly higher SUVmax in EOMs compared to those receiving symptomatic treatment (P < 0.01).</p><p><strong>Conclusions: </strong>[<sup>68</sup>Ga]DOTATATE PET/CT is a reliable method for assessing the inflammatory activity of EOMs in TAO patients, providing strong objective evidence for the precise diagnosis and treatment.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"120-130"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan A Azcona, Anja S Wacker, Chul-Hee Lee, Edward K Fung, Thomas M Jeitner, Onorina L Manzo, Annarita Di Lorenzo, John W Babich, Alejandro Amor-Coarasa, James M Kelly
{"title":"2-[<sup>18</sup>F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.","authors":"Juan A Azcona, Anja S Wacker, Chul-Hee Lee, Edward K Fung, Thomas M Jeitner, Onorina L Manzo, Annarita Di Lorenzo, John W Babich, Alejandro Amor-Coarasa, James M Kelly","doi":"10.1007/s11307-024-01978-y","DOIUrl":"10.1007/s11307-024-01978-y","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA). Therefore, we explored the utility of 2-[<sup>18</sup>F]fluoropropionic acid ([<sup>18</sup>F]FPA), an SCFA analog, as an imaging biomarker of cardiac injury in mice exposed to doxorubicin.</p><p><strong>Procedures: </strong>Cardiotoxicity and cardiac dysfunction were induced in mice by an 8-dose regimen of doxorubicin (cumulative dose 24 mg/kg) administered over 14 days. The effects of doxorubicin exposure were assessed by measurement of heart weights, left ventricular ejection fractions, and blood cardiac troponin levels. Whole body and cardiac [<sup>18</sup>F]FPA uptakes were determined by PET and tissue gamma counting in the presence or absence of AZD3965, a pharmacological inhibitor of monocarboxylate transporter 1 (MCT1). Radiation absorbed doses were estimated using tissue time-activity concentrations.</p><p><strong>Results: </strong>Significantly higher cardiac [<sup>18</sup>F]FPA uptake was observed in doxorubicin-treated animals. This uptake remained constant from 30 to 120 min post-injection. Pharmacological inhibition of MCT1-mediated transport by AZD3965 selectively decreased the uptake of [<sup>18</sup>F]FPA in tissues other than the heart. Co-administration of [<sup>18</sup>F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity.</p><p><strong>Conclusions: </strong>[<sup>18</sup>F]FPA, especially when co-administered with AZD3965, is a new tool for imaging changes in fatty acid metabolism occurring in response to doxorubicin-induced cardiomyopathy by PET.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"109-119"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irene Canavesi, Navin Viswakarma, Boris Epel, Mrignayani Kotecha
{"title":"In Vivo Mouse Abdominal Oxygen Imaging And Assessment of Subcutaneously Implanted Beta Cell Replacement Devices.","authors":"Irene Canavesi, Navin Viswakarma, Boris Epel, Mrignayani Kotecha","doi":"10.1007/s11307-024-01963-5","DOIUrl":"10.1007/s11307-024-01963-5","url":null,"abstract":"<p><strong>Purpose: </strong>Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing pancreatic beta cells. Beta cell replacement devices or bioartificial pancreas (BAP) have shown promise in curing T1D and providing long-term insulin independence without the need for immunosuppressants. Hypoxia in BAP devices damages cells and imposes limitations on device dimensions. Noninvasive in vivo oxygen imaging assessment of implanted BAP devices will provide the necessary feedback and improve the chances of success. Pulse-mode electron paramagnetic resonance (EPR) oxygen imaging (EPROI) using injectable trityl OX071 as the oxygen-sensitive agent is an excellent technique for obtaining partial oxygen pressure (pO<sub>2</sub>) maps in vitro and in vivo. In this study, our goal was to optimize in vivo mouse abdominal EPROI and demonstrate proof-of-concept pO<sub>2</sub> imaging of subcutaneously implanted BAP devices.</p><p><strong>Methods: </strong>All EPROI experiments were performed using a 25 mT EPROI instrument, JIVA-25®. For in vivo EPROI experiments, trityl OX071, a whole-body mouse resonator (∅32 mm × 35 mm), C57BL6 mice, and the inversion recovery electron spin echo (IRESE) pulse sequence were utilized. We investigated the signal amplitude and pO<sub>2</sub> in mouse abdomen region for intravenous (i.v.) and intraperitoneal (i.p.) injection methods with either only a single bolus (B) or bolus plus infusion (BI) for 72.2 mM OX071 and the effect of OX071 concentrations from 18 to 72.2 mM for the i.p.-B injection method. We also investigated the impact of animal respiratory rate on mouse abdominal pO<sub>2</sub>. Finally, we performed proof-of-concept pO<sub>2</sub> imaging of two subcutaneously implanted BAP devices, OxySite and TheraCyte. At the end of the four-week study, the TheraCyte devices were extracted and analyzed for fibrosis, vascular differentiation, and immune cell infiltration.</p><p><strong>Results: </strong>We established that mouse abdominal pO<sub>2</sub> remains stable irrespective of trityl injection methods, concentrations, imaging time, or animal breathing rate. We demonstrate that the i.p.-B and i.p.-BI methods are suitable for EPROI, and i.p.-B method provides higher signal amplitude compared to i.v.-BI and up to 75 min of imaging. An injection with a reduced trityl concentration and higher volume provides higher signal amplitude for i.p.-B method at the beginning. We also highlight the advantage of milder anesthesia for consistent, reliable mouse pO<sub>2</sub> imaging. Finally, we demonstrate that EPROI could provide longitudinal noninvasive oxygen assessment of subcutaneously implanted BAP devices in vivo.</p><p><strong>Conclusions: </strong>In vivo EPROI is a reliable technique for mouse abdominal oxygen imaging and longitudinal assessment of subcutaneously implanted BAP devices noninvasively. This work reports abdominal oxygen imaging in the mouse model and demonstrates its application ","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"64-77"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Visions by WIMIN: Imposter Phenomenon.","authors":"Eman Akam-Baxter, Christine M O'Brien, Sanhita Sinharay, Veronica Clavijo-Jordan, Susana Bulnes Rodriguez, Jenny Nneka Ijoma, Anmol Kustagi, Mahnue Sahn, Fatoumata Diop, Kyeara Mack, Natasha Malonza, Natalia Herrero Alvarez","doi":"10.1007/s11307-024-01971-5","DOIUrl":"10.1007/s11307-024-01971-5","url":null,"abstract":"<p><p>The imposter phenomenon (IP) is a destructive set of beliefs, traits, and experiences in which high-achieving individuals fail to internalize their accomplishments and falsely perceive themselves as frauds. IP is a function of underrepresentation and contributes to and perpetuates a cycle of low self-worth, perfectionism, and anxiety, all of which negatively affect job performance and reinforce the IP cycle. Mitigating the deleterious effects of IP requires first naming this phenomenon and recognizing the patterns of IP. In this article, we summarize pertinent social science literature on this topic and share experiences of IP as told by the authors and anonymous contributors. We highlight the potential destructive effects of IP, as well as strategies that mentors and trainees can utilize to counter this phenomenon.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"17-22"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isaac Shiri, Yazdan Salimi, Pooya Mohammadi Kazaj, Sara Bagherieh, Mehdi Amini, Abdollah Saberi Manesh, Habib Zaidi
{"title":"Deep Radiogenomics Sequencing for Breast Tumor Gene-Phenotype Decoding Using Dynamic Contrast Magnetic Resonance Imaging.","authors":"Isaac Shiri, Yazdan Salimi, Pooya Mohammadi Kazaj, Sara Bagherieh, Mehdi Amini, Abdollah Saberi Manesh, Habib Zaidi","doi":"10.1007/s11307-025-01981-x","DOIUrl":"10.1007/s11307-025-01981-x","url":null,"abstract":"<p><strong>Purpose: </strong>We aim to perform radiogenomic profiling of breast cancer tumors using dynamic contrast magnetic resonance imaging (MRI) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) genes.</p><p><strong>Methods: </strong>The dataset used in the current study consists of imaging data of 922 biopsy-confirmed invasive breast cancer patients with ER, PR, and HER2 gene mutation status. Breast MR images, including a T1-weighted pre-contrast sequence and three post-contrast sequences, were enrolled for analysis. All images were corrected using N4 bias correction algorithms. Based on all images and tumor masks, a bounding box of 128 × 128 × 68 was chosen to include all tumor regions. All networks were implemented in 3D fashion with input sizes of 128 × 128 × 68, and four images were input to each network for multi-channel analysis. Data were randomly split into train/validation (80%) and test set (20%) with stratification in class (patient-wise), and all metrics were reported in 20% of the untouched test dataset.</p><p><strong>Results: </strong>For ER prediction, SEResNet50 achieved an AUC mean of 0.695 (CI95%: 0.610-0.775), a sensitivity of 0.564, and a specificity of 0.787. For PR prediction, ResNet34 achieved an AUC mean of 0.658 (95% CI: 0.573-0.741), a sensitivity of 0.593, and a specificity of 0.734. For HER2 prediction, SEResNext101 achieved an AUC mean of 0.698 (95% CI: 0.560-0.822), a sensitivity of 0.750, and a specificity of 0.625.</p><p><strong>Conclusion: </strong>The current study demonstrated the feasibility of imaging gene-phenotype decoding in breast tumors using MR images and deep learning algorithms with moderate performance.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"32-43"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Izquierdo-Garcia, Pauline Désogère, Anne L Philip, David E Sosnovik, Ciprian Catana, Peter Caravan
{"title":"First-in-human Evaluation of Safety and Dosimetry of [<sup>64</sup>Cu]FBP8: A fibrin-binding PET Probe.","authors":"David Izquierdo-Garcia, Pauline Désogère, Anne L Philip, David E Sosnovik, Ciprian Catana, Peter Caravan","doi":"10.1007/s11307-024-01973-3","DOIUrl":"10.1007/s11307-024-01973-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [<sup>64</sup>Cu]Fibrin Binding Probe #8 ([<sup>64</sup>Cu]FBP8) in healthy subjects. [<sup>64</sup>Cu]FBP8-PET previously demonstrated its potential in two recent applications: thrombus imaging and pulmonary fibrosis.</p><p><strong>Procedures: </strong>This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [<sup>64</sup>Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 h, 4 h and 24 h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software.</p><p><strong>Results: </strong>Subjects were injected with 400 MBq of [<sup>64</sup>Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [<sup>64</sup>Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG, 0.020mSv/MBq).</p><p><strong>Conclusions: </strong>This study demonstrates the following properties of the [<sup>64</sup>Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 min in a single session. These properties provide the basis for [<sup>64</sup>Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"99-108"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"2024 World Molecular Imaging Congress Program.","authors":"","doi":"10.1007/s11307-024-01977-z","DOIUrl":"10.1007/s11307-024-01977-z","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"761-1256"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayon Nandi, Masayoshi Nakano, James Robert Brašić, Zabecca S Brinson, Kelly Kitzmiller, Anil Mathur, Mona Mohamed, Joshua Roberts, Dean F Wong, Hiroto Kuwabara
{"title":"Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.","authors":"Ayon Nandi, Masayoshi Nakano, James Robert Brašić, Zabecca S Brinson, Kelly Kitzmiller, Anil Mathur, Mona Mohamed, Joshua Roberts, Dean F Wong, Hiroto Kuwabara","doi":"10.1007/s11307-024-01947-5","DOIUrl":"10.1007/s11307-024-01947-5","url":null,"abstract":"<p><strong>Purpose: </strong>Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP<sub>ND</sub>) in rodent PET studies.</p><p><strong>Procedures: </strong>PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[<sup>18</sup>F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([<sup>18</sup>F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BP<sub>ND</sub> in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT.</p><p><strong>Results: </strong>The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BP<sub>ND</sub> in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter.</p><p><strong>Conclusions: </strong>The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BP<sub>ND</sub> in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1016-1026"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rohini Bijjam, Susan Shorter, Alison M Bratt, Valerie B O'Leary, Vasilis Ntziachristos, Saak Victor Ovsepian
{"title":"Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.","authors":"Rohini Bijjam, Susan Shorter, Alison M Bratt, Valerie B O'Leary, Vasilis Ntziachristos, Saak Victor Ovsepian","doi":"10.1007/s11307-024-01954-6","DOIUrl":"10.1007/s11307-024-01954-6","url":null,"abstract":"<p><p>Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"912-925"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}