Molecular Imaging and Biology最新文献

{"title":"The Potential Utility of (2S,4R)-4-[¹⁸F]fluoroglutamine as a Novel Metabolic Imaging Marker for Inflammation Explored by Rat Models of Arthritis and Paw Edema.","authors":"Min-Jeong Kim, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu","doi":"10.1007/s11307-024-01967-1","DOIUrl":"10.1007/s11307-024-01967-1","url":null,"abstract":"<p><strong>Purpose: </strong>(2S,4R)-4-[¹⁸F]fluoroglutamine ([¹⁸F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [¹⁸F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA).</p><p><strong>Procedures: </strong>The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [¹⁸F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 min under anesthesia with isoflurane. The standard uptake value of [¹⁸F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET.</p><p><strong>Results: </strong>The CIPE models showed a trend toward higher uptake in the injected paw compared to the non-injected paw (P = 0.068). In CIA models, uptake in the paws with severe inflammation was significantly higher than the controls (P = 0.011), while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [¹⁸F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (r = 0.88, P = 0.009). The pathological findings confirmed profound inflammation in CIA.</p><p><strong>Conclusions: </strong>[¹⁸F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"10-16"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687723","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":"Ex Vivo Human Tissue Functions as a Testing Platform for the Evaluation of a Nerve-Specific Fluorophore.","authors":"Logan M Bateman, Samuel S Streeter, Kendra A Hebert, Dylan J Parker, Kaye Obando, Kiara Sherlin Salas Moreno, George J Zanazzi, Connor W Barth, Lei G Wang, Summer L Gibbs, Eric R Henderson","doi":"10.1007/s11307-024-01968-0","DOIUrl":"10.1007/s11307-024-01968-0","url":null,"abstract":"<p><strong>Significance: </strong>Selecting a nerve-specific lead fluorescent agent for translation in fluorescence-guided surgery is time-consuming and expensive. Preclinical fluorescent agent studies rely primarily on animal models, which are a critical component of preclinical testing, but these models may not predict fluorophore performance in human tissues.</p><p><strong>Aim: </strong>The primary aim of this study was to evaluate and compare two preclinical models to test tissue-specific fluorophores based on discarded human tissues. The secondary aim was to use these models to determine the ability of a molecularly targeted fluorophore, LGW16-03, to label ex vivo human nerve tissues.</p><p><strong>Approach: </strong>Patients undergoing standard-of-care transtibial or transfemoral amputation were consented and randomized to topical or systemic administration of LGW16-03 following amputation. After probe administration, nerves and background tissues were surgically resected and imaged to determine nerve fluorescence signal-to-background tissue ratio (SBR) and signal-to-noise ratio (SNR) metrics. Analysis of variance (ANOVA) determined statistical differences in metric means between administration cohorts and background tissue groups. Receiver operating characteristic (ROC) curve-derived statistics quantified the discriminatory performance of LGW16-03 fluorescence for labeling nerve tissues.</p><p><strong>Results: </strong>Tissue samples from 18 patients were analyzed. Mean nerve-to-adipose SBR was greater than nerve-to-muscle SBR (p = 0.001), but mean nerve-to-adipose SNR was not statistically different from mean nerve-to-muscle SNR (p = 0.069). Neither SBR nor SNR means were statistically different between fluorophore administration cohorts (p ≥ 0.448). When administration cohorts were combined, nerve-to-adipose SBR was greater than nerve-to-muscle SBR (mean ± standard deviation; 4.2 ± 2.9 vs. 1.8 ± 1.9; p < 0.001), but SNRs for nerve-to-adipose and nerve-to-muscle were not significantly different (5.1 ± 4.0 vs. 3.1 ± 3.4; p = 0.055). ROC curve-derived statistics to quantify LGW16-03 nerve labeling performance varied widely between patients, with sensitivities and specificities ranging from 0.2-99.9% and 0.4-100.0%.</p><p><strong>Conclusion: </strong>Systemic and topical administration of LGW16-03 yielded similar fluorescence labeling of nerve tissues. Both administration approaches provided nerve-specific contrast similar to that observed in preclinical animal models. Fluorescence contrast was generally higher for nerve-to-adipose versus nerve-to-muscle. Ex vivo human tissue models provide safe evaluation of fluorophores in the preclinical phase and can aid in the selection of lead agents prior to first-in-human trials.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"23-31"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807580","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":"⁶⁸Ga-PSMA PET/CT-Based Model Predicts Perineural Invasion of Prostate Cancer with Whole-Mount Sections.","authors":"Jie Gao, Yao Fu, Kuiqiang He, Qinfeng Xu, Feng Wang, Hongqian Guo","doi":"10.1007/s11307-024-01974-2","DOIUrl":"10.1007/s11307-024-01974-2","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a novel risk model incorporating ⁶⁸Ga-PSMA PET/CT parameters for prediction of perineural invasion (PNI) of prostate cancer (PCa).</p><p><strong>Methods: </strong>The study retrospectively enrolled 192 PCa patients with preoperative multiparametric MRI, ⁶⁸Ga-PSMA PET/CT and radical specimen. Imaging parameters were derived from both mpMRI and PET/CT images. S100 immunohistochemistry staining was conducted to evaluate PNI of PCa. Significant predictors were derived with univariate and multivariate logistic regression analyses, and the PNI-risk nomogram was constructed with significant predictors. Internal discrimination validation was performed with receiver operating characteristic analysis. Calibration curves were plotted, decision curve and clinical impact curve analysis were performed for clinical benefit exploration.</p><p><strong>Results: </strong>With the median peritumoral nerve density of 6, patients were stratified as low-PNI group (nerve density < 6, n = 78, 40.6%) and high-PNI group (nerve density ≥ 6, n = 114, 59.4%). Compared with low-PNI PCa, high-PNI PCa harbored significantly larger imaging lesion diameter (P < 0.001), higher PI-RADS score (P = 0.009), higher SUVmax (P < 0.001), larger tumor diameter (P = 0.024) and higher Gleason grade group (P < 0.001). Further, with univariate and multivariate analyses, imaging lesion diameter (OR 2.98, 95% CI 1.73-5.16, P = 0.004) and SUVmax (OR 3.59, 95%CI 2.32-5.55, P < 0.001) and were identified as independent predictors for PNI in PCa, and a PNI-risk nomogram incorporating these two predictors was constructed. The PNI-risk nomogram demonstrated considerable calibration (mean absolute error 0.026) and discrimination (area under the curve = 0.889, sensitivity 73.1%, specificity 97.4%) abilities, harboring net benefits with threshold probabilities range from 0 to 0.80.</p><p><strong>Conclusion: </strong>⁶⁸Ga-PSMA PET/CT-based model could effectively predict the perineural invasion of PCa. These results may help with the decision-making on active surveillance, focal therapy and surgery approach. Additionally, patients suspicious of high-density PNI PCa should receive more radical treatment than low-PNI PCa.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"44-53"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837613","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":"PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [¹⁸F]TZ4877 in Nonhuman Primates.","authors":"Jiwei Gu, Ming-Qiang Zheng, Daniel Holden, Krista Fowles, Lin Qiu, Zachary Felchner, Li Zhang, Jim Ropchan, Robert J Gropler, Richard E Carson, Zhude Tu, Yiyun Huang, Ansel T Hillmer","doi":"10.1007/s11307-024-01979-x","DOIUrl":"10.1007/s11307-024-01979-x","url":null,"abstract":"<p><strong>Purpose: </strong>The sphingosine-1-phosphate receptor-1 (S1PR₁) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR₁-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR₁ radiotracer, [¹⁸F]TZ4877, in nonhuman primates.</p><p><strong>Procedures: </strong>[¹⁸F]TZ4877 was produced via nucleophilic substitution of tosylate precursor with K[¹⁸F]/F^- followed by deprotection. Brain PET imaging data were acquired with a Focus220 scanner in two Macaca mulatta (6, 13 years old) for 120-180 min following bolus injection of 118-163 MBq [¹⁸F]TZ4877, with arterial blood sampling and metabolite analysis to measure the parent input function and plasma free fraction (f_P). Each animal was scanned at baseline, 15-18 min after 0.047-0.063 mg/kg of the S1PR₁ inhibitor ponesimod, 33 min after 0.4-0.8 mg/kg of the S1PR₁-specific compound TZ82112, and 167-195 min after 1 ng/kg of the immune stimulus endotoxin. Kinetic analysis with metabolite-corrected input function was performed to estimate the free fraction corrected total distribution volume (V_T/f_P). Whole-body dosimetry scans were acquired in 2 animals (1M, 1F) with a Biograph Vision PET/CT System, and absorbed radiation dose estimates were calculated with OLINDA.</p><p><strong>Results: </strong>[¹⁸F]TZ4877 exhibited fast kinetics that were described by the reversible 2-tissue compartment model. Baseline [¹⁸F]TZ4877 f_P was low (<1%), and [¹⁸F]TZ4877 V_T/f_P values were 233-866 mL/cm³. TZ82112 dose-dependently reduced [¹⁸F]TZ4877 V_T/f_P, while ponesimod and endotoxin exhibited negligible effects on V_T/f_P, possibly due to scan timing relative to dosing. Dosimetry studies identified the critical organs of gallbladder (0.42 (M) and 0.31 (F) mSv/MBq) for anesthetized nonhuman primate.</p><p><strong>Conclusions: </strong>[¹⁸F]TZ4877 exhibits reversible kinetic properties, but the low f_P value limits reproducible quantification with this radiotracer. S1PR₁ is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"54-63"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951856","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":"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 × 10⁶) 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 × 10⁴ 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 × 10⁷ 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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Brain Impairment Using Proton Exchange Rate MRI in a Kainic Acid-Induced Rat Model of Epilepsy.","authors":"Huanhuan Yang, Qiting Wu, Lin Li, Yin Wu","doi":"10.1007/s11307-024-01980-4","DOIUrl":"10.1007/s11307-024-01980-4","url":null,"abstract":"<p><strong>Purpose: </strong>Proton exchange rate (K_ex) is a valuable biophysical metric. K_ex MRI may augment conventional structural MRI by revealing brain impairments at the molecular level. This study aimed to investigate the feasibility of K_ex MRI in evaluating brain injuries at multiple epilepsy stages.</p><p><strong>Procedures: </strong>Six adult rats with epilepsy induced by intra-amygdalae administration of kainic acid (KA) underwent MRI experiment at 11.7 T. Two MRI scans, including T₁ mapping and CEST imaging under three B₁ amplitudes of 0.75, 1.0, and 1.5 μT, were conducted before and 2, 7, and 28 days after KA injection. Quasi-steady-state analysis was performed to reconstruct equilibrium Z spectra. Direct saturation was resolved using a multi-pool Lorentzian model and removed from Z spectra. The residual spectral signal (ΔZ) was used to construct the omega plot of (1-ΔZ)/ΔZ as a linear function of 1/ <math><msubsup><mi>ω</mi> <mrow><mn>1</mn></mrow> <mn>2</mn></msubsup> </math> , from which K_ex was quantified from the X-axis intercept. One-way ANOVA or two-tailed paired student's t-test was employed with P < 0.05 as statistically significant.</p><p><strong>Results: </strong>All animals exhibited repetitive status epilepticus with IV to V seizure stages after KA injection. At day 28, K_ex values in the hippocampus and cerebral cortex at the surgical hemisphere with KA injection were significantly higher than that at the time points of control and/or day 2 in the same regions (P < 0.01). Moreover, the values were significantly higher than that in respective contralateral regions at day 28 (P < 0.02). No substantial changes of K_ex were seen in bilateral thalamus or contralateral hemisphere among time points (all P > 0.05).</p><p><strong>Conclusions: </strong>K_ex increase significantly in the cerebral cortex and hippocampus at the surgical hemisphere, especially at day 28, likely due to substantial alterations at chronic epilepsy stage. K_ex MRI is promising to evaluate brain impairment, facilitating the diagnosis and evaluation of neurological disorders.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922100","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":"¹⁸F-FAPI-42 PET/CT and ¹⁸F-FDG PET/CT in Patients with Malignant Digestive System Neoplasms: A Head-to-Head Comparative Study.","authors":"Min Xiong, HongJi You, Jingmin Feng, Yipei Liu, Xiaoming Luo, Ying Liu, Sheng-Nan Jiang","doi":"10.1007/s11307-025-01982-w","DOIUrl":"10.1007/s11307-025-01982-w","url":null,"abstract":"<p><strong>Purpose: </strong>Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of ¹⁸F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) PET/CT in primary and metastatic lesions in patients with malignant digestive system neoplasms and to determine the potential clinical benefit.</p><p><strong>Procedures: </strong>Forty-two patients (men = 30, women = 12, mean age = 56.71 ± 13.26 years) who underwent ¹⁸F-FDG PET/CT and ¹⁸F-FAPI-42 PET/CT simultaneously for diagnosis, staging, and restaging were enrolled. Quantitative data, including standardized uptake value (SUV), tumor-to-liver ratio (TLR), and tumor-to-blood pool ratio (TBR), were analyzed. Two independent readers performed a visual assessment of lesion number and location on PET/CT images. Interobserver agreement between two examinations was calculated using Cohen's kappa (κ).</p><p><strong>Results: </strong>Primary tumor locations included the liver (n = 20), stomach (n = 9), pancreas (n = 5), and intestine (n = 10). More intense ¹⁸F-FAPI-42 uptake and higher tumor-to-background contrast were detected in most primary and metastatic lesions compared with ¹⁸F-FDG, contributing to improved diagnostic accuracy ranging from 95.24% to 100%. Moreover, additional lesions showing ¹⁸F-FAPI-42 uptake in primary, locoregional and distant metastatic lesions were visualized, especially in multiple liver and peritoneal metastases. Patient-based interobserver agreement varied from moderate to strong, with suboptimal outcomes observed in primary tumors (κ = 0.441, P = 0.01) and preferable results derived from metastatic liver and bone lesions (κ = 1 and 0.896, both P < 0.01). ¹⁸F-FAPI-42 PET/CT resulted in modified treatment strategies for 40.48% (17/42) of patients, while ¹⁸F-FDG PET/CT led to altered therapeutic regimens in only 4.8% (2/42) of patients.</p><p><strong>Conclusions: </strong>In selected patients with malignant digestive system neoplasms, our study shows that ¹⁸F-FAPI-42 PET/CT is a promising alternative for assessing primary tumors and metastases and aiding staging, restaging, and decision-making, with higher uptake and better lesion visualization compared with ¹⁸F-FDG. Additionally, it may shed light into the treatment selection and response assessment for FAP-targeted therapy or immunotherapy.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"131-141"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978782","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":"Evaluation of Inflammatory Activity of Extraocular Muscles in Thyroid Associated Orbitopathy by [⁶⁸Ga]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 [⁶⁸Ga]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 [⁶⁸Ga]DOTATATE PET/CT. Among these, 18 patients underwent orbital [^99mTc]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>[⁶⁸Ga]DOTATATE PET/CT could effectively evaluate the inflammatory activity of the EOMs in TAO patients and demonstrate good consistency with [^99mTc]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>[⁶⁸Ga]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}

{"title":"2-[¹⁸F]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-[¹⁸F]fluoropropionic acid ([¹⁸F]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 [¹⁸F]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 [¹⁸F]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 [¹⁸F]FPA in tissues other than the heart. Co-administration of [¹⁸F]FPA and AZD3965 enhanced the imaging contrast of the diseased heart while reducing overall exposure to radioactivity.</p><p><strong>Conclusions: </strong>[¹⁸F]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}

{"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":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;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&lt;sub&gt;2&lt;/sub&gt;) 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&lt;sub&gt;2&lt;/sub&gt; imaging of subcutaneously implanted BAP devices.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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&lt;sub&gt;2&lt;/sub&gt; 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&lt;sub&gt;2&lt;/sub&gt;. Finally, we performed proof-of-concept pO&lt;sub&gt;2&lt;/sub&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We established that mouse abdominal pO&lt;sub&gt;2&lt;/sub&gt; 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&lt;sub&gt;2&lt;/sub&gt; imaging. Finally, we demonstrate that EPROI could provide longitudinal noninvasive oxygen assessment of subcutaneously implanted BAP devices in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;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}