Molecular Imaging最新文献

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Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using 99mTc-MAG3-Cet-F(ab')2-Based SPECT/CT Imaging. 使用基于99mTc-MAG3-Cet-F(ab')2的SPECT/CT成像无创评估消化道肿瘤EGFR表达
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-06-24 eCollection Date: 2022-01-01 DOI: 10.1155/2022/3748315
Dai Shi, Yiqiu Zhang, Zhan Xu, Zhan Si, Yuan Cheng, Dengfeng Cheng, Guobing Liu
{"title":"Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub>-Based SPECT/CT Imaging.","authors":"Dai Shi,&nbsp;Yiqiu Zhang,&nbsp;Zhan Xu,&nbsp;Zhan Si,&nbsp;Yuan Cheng,&nbsp;Dengfeng Cheng,&nbsp;Guobing Liu","doi":"10.1155/2022/3748315","DOIUrl":"https://doi.org/10.1155/2022/3748315","url":null,"abstract":"<p><strong>Purpose: </strong>This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')<sub>2</sub> fragment- (Cet-F(ab')<sub>2</sub>-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models.</p><p><strong>Methods: </strong>Cet-F(ab')<sub>2</sub> was synthesized using immunoglobulin G-degrading enzyme of <i>Streptococcus pyogenes</i> (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab')<sub>2</sub> was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab')<sub>2</sub> was conjugated with NHS-MAG<sub>3</sub> for <sup>99m</sup>Tc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub> tracer. Furthermore, <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub> SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice.</p><p><strong>Results: </strong>HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab')<sub>2</sub> and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab')<sub>2</sub> and <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub> showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29 ± 5.72, <i>n</i> = 4) after tracer injection. The <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub>-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro.</p><p><strong>Conclusion: </strong>SPECT/CT imaging using <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub> enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"3748315"},"PeriodicalIF":2.8,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40556105","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}
引用次数: 1
In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [18F]Me4FDG PET in Rats. [18F]Me4FDG PET在大鼠体内评价钠-葡萄糖共转运体(SGLTs)的功能
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-06-21 eCollection Date: 2022-01-01 DOI: 10.1155/2022/4635171
Yohji Matsusaka, Xinyu Chen, Paula Arias-Loza, Rudolf A Werner, Naoko Nose, Takanori Sasaki, Steven P Rowe, Martin G Pomper, Constantin Lapa, Takahiro Higuchi
{"title":"In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [<sup>18</sup>F]Me4FDG PET in Rats.","authors":"Yohji Matsusaka,&nbsp;Xinyu Chen,&nbsp;Paula Arias-Loza,&nbsp;Rudolf A Werner,&nbsp;Naoko Nose,&nbsp;Takanori Sasaki,&nbsp;Steven P Rowe,&nbsp;Martin G Pomper,&nbsp;Constantin Lapa,&nbsp;Takahiro Higuchi","doi":"10.1155/2022/4635171","DOIUrl":"https://doi.org/10.1155/2022/4635171","url":null,"abstract":"<p><strong>Background: </strong>Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[<sup>18</sup>F]fluoro-D-glucopyranoside ([<sup>18</sup>F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport.</p><p><strong>Methods: </strong>We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose ([<sup>18</sup>F]FDG), or the SGLT-targeting agent, [<sup>18</sup>F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [<sup>18</sup>F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV).</p><p><strong>Results: </strong>Serving as reference, intestinal administration of [<sup>18</sup>F]FDG led to slow absorption with retention of 89.2 ± 3.5% of administered radioactivity at 15 min. [<sup>18</sup>F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of 18.5 ± 1.2% (<i>P</i> < 0.0001). Intraintestinal phlorizin led to marked increase of [<sup>18</sup>F]Me4FDG uptake (15 min, 99.9 ± 4.7%; <i>P</i> < 0.0001 vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [<sup>18</sup>F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, 0.42 ± 0.10 vs. untreated controls, 1.20 ± 0.03; <i>P</i> < 0.0001).</p><p><strong>Conclusion: </strong>As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [<sup>18</sup>F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [<sup>18</sup>F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"4635171"},"PeriodicalIF":2.8,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40571733","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}
引用次数: 1
Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [18F]FEPPA: A Feasibility Study. PET显示低浓度pm2.5暴露大鼠神经炎症通过改进的自动化生产[18F]FEPPA:可行性研究。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-06-07 eCollection Date: 2022-01-01 DOI: 10.1155/2022/1076444
Mei-Fang Cheng, Tsun-Jen Cheng, Yue Leon Guo, Ching-Hung Chiu, Hung-Ming Wu, Ruoh-Fang Yen, Ya-Yao Huang, Wen-Sheng Huang, Chyng-Yann Shiue
{"title":"Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [<sup>18</sup>F]FEPPA: A Feasibility Study.","authors":"Mei-Fang Cheng,&nbsp;Tsun-Jen Cheng,&nbsp;Yue Leon Guo,&nbsp;Ching-Hung Chiu,&nbsp;Hung-Ming Wu,&nbsp;Ruoh-Fang Yen,&nbsp;Ya-Yao Huang,&nbsp;Wen-Sheng Huang,&nbsp;Chyng-Yann Shiue","doi":"10.1155/2022/1076444","DOIUrl":"https://doi.org/10.1155/2022/1076444","url":null,"abstract":"<p><strong>Background: </strong>[<sup>18</sup>F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats.</p><p><strong>Results: </strong>Using this automated synthesis method, the RCY of the [<sup>18</sup>F]FEPPA was 38 ± 4% (<i>n</i> = 17, EOB) in a synthesis time of 83 ± 8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138 GBq/<i>μ</i>mol (EOS, <i>n</i> = 15), respectively. The quality of the [<sup>18</sup>F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [<sup>18</sup>F]FEPPA was stable at 21 ± 2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [<sup>18</sup>F]FEPPA in the brain of PM2.5-exposed rats (<i>n</i> = 6) were higher than that of normal controls (<i>n</i> = 6) and regional-specific.</p><p><strong>Conclusions: </strong>Using the improved semipreparative HPLC purification, [<sup>18</sup>F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"1076444"},"PeriodicalIF":2.8,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40556106","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}
引用次数: 1
Celecoxib-Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by 89Zr Immuno-PET. 塞来昔布诱导的结肠癌CD133表达调节通过AKT抑制发生,并通过89Zr免疫pet监测。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-01-07 eCollection Date: 2022-01-01 DOI: 10.1155/2022/4906934
Kyung-Ho Jung, Jin Hee Lee, Mina Kim, Eun Ji Lee, Young Seok Cho, Kyung-Han Lee
{"title":"Celecoxib-Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by <sup>89</sup>Zr Immuno-PET.","authors":"Kyung-Ho Jung,&nbsp;Jin Hee Lee,&nbsp;Mina Kim,&nbsp;Eun Ji Lee,&nbsp;Young Seok Cho,&nbsp;Kyung-Han Lee","doi":"10.1155/2022/4906934","DOIUrl":"https://doi.org/10.1155/2022/4906934","url":null,"abstract":"<p><p>We developed an immuno-PET technique that monitors modulation of tumor CD133 expression, which is required for the success of CD133-targeted therapies. <i>Methods</i>. Anti-CD133 antibodies were subjected to sulfhydryl moiety-specific <sup>89</sup>Zr conjugation. <sup>89</sup>Zr-CD133 IgG was evaluated for specific activity and radiolabel stability. Colon cancer cells underwent binding assays and Western blotting. Biodistribution and PET studies were performed in mice. <i>Results</i>. <sup>89</sup>Zr-CD133 IgG showed excellent target specificity with 97.2 ± 0.7% blocking of HT29 cell binding by an excess antibody. Intravenous <sup>89</sup>Zr-CD133 IgG followed biexponential blood clearance and showed CD133-specific uptake in HT29 tumors. <sup>89</sup>Zr-CD133 IgG PET/CT and biodistribution studies confirmed high HT29 tumor uptake with lower activities in the blood and normal organs. In HT29 cells, celecoxib dose-dependently decreased CD133 expression and <sup>89</sup>Zr-CD133 IgG binding that reached 19.9 ± 2.1% (<i>P</i> < 0.005) and 50.3 ± 10.9% (<i>P</i> < 0.001) of baseline levels by 50 <i>μ</i>M, respectively. Celecoxib treatment of mice significantly suppressed tumor CD133 expression to 67.5 ± 7.8% of controls (<i>P</i> < 0.005) and reduced tumor <sup>89</sup>Zr-CD133 IgG uptake from 15.5 ± 1.4% at baseline to 12.3 ± 2.0%ID/g (<i>P</i> < 0.01). Celecoxib-induced CD133 reduction in HT29 cells and tumors was associated with substantial suppression of AKT activation. There were also reduced HIF-1<i>α</i> accumulation and I<i>κ</i>B<i>α</i>/NF<i>κ</i>B phosphorylation. <i>Conclusion</i>. <sup>89</sup>Zr-CD133 IgG PET provides high-contrast tumor imaging and monitors celecoxib treatment-induced modulation of tumor CD133 expression, which was found to occur through AKT inhibition. This technique may thus be useful for screening drugs that can effectively suppress colon cancer stem cells.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"4906934"},"PeriodicalIF":2.8,"publicationDate":"2022-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39885954","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}
引用次数: 5
Compressed Sensing Photoacoustic Imaging Reconstruction Using Elastic Net Approach. 基于弹性网方法的压缩传感光声成像重建。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-01-01 DOI: 10.1155/2022/7877049
Xueyan Liu, Shuo Dai, Mengyu Wang, Yining Zhang
{"title":"Compressed Sensing Photoacoustic Imaging Reconstruction Using Elastic Net Approach.","authors":"Xueyan Liu,&nbsp;Shuo Dai,&nbsp;Mengyu Wang,&nbsp;Yining Zhang","doi":"10.1155/2022/7877049","DOIUrl":"https://doi.org/10.1155/2022/7877049","url":null,"abstract":"<p><p>Photoacoustic imaging involves reconstructing an estimation of the absorbed energy density distribution from measured ultrasound data. The reconstruction task based on incomplete and noisy experimental data is usually an ill-posed problem that requires regularization to obtain meaningful solutions. The purpose of the work is to propose an elastic network (EN) model to improve the quality of reconstructed photoacoustic images. To evaluate the performance of the proposed method, a series of numerical simulations and tissue-mimicking phantom experiments are performed. The experiment results indicate that, compared with the <i>L</i> <sub>1</sub>-norm and <i>L</i> <sub>2</sub>-normbased regularization methods with different numerical phantoms, Gaussian noise of 10-50 dB, and different regularization parameters, the EN method with <i>α</i> = 0.5 has better image quality, calculation speed, and antinoise ability.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"2022 ","pages":"7877049"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9881674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10650670","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}
引用次数: 0
Preclinical Evaluation of an Activity-Based Probe for Intraoperative Imaging of Esophageal Cancer. 基于活动的食管癌术中成像探针的临床前评价。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-01-01 DOI: 10.1155/2022/5447290
Gregory T Kennedy, Feredun S Azari, Bilal Nadeem, Ashley Chang, Alix Segil, Elizabeth Bernstein, Charuhas Desphande, John C Kucharczuk, Edward J Delikatny, Sunil Singhal
{"title":"Preclinical Evaluation of an Activity-Based Probe for Intraoperative Imaging of Esophageal Cancer.","authors":"Gregory T Kennedy,&nbsp;Feredun S Azari,&nbsp;Bilal Nadeem,&nbsp;Ashley Chang,&nbsp;Alix Segil,&nbsp;Elizabeth Bernstein,&nbsp;Charuhas Desphande,&nbsp;John C Kucharczuk,&nbsp;Edward J Delikatny,&nbsp;Sunil Singhal","doi":"10.1155/2022/5447290","DOIUrl":"https://doi.org/10.1155/2022/5447290","url":null,"abstract":"<p><strong>Background: </strong>Early detection and complete resection are important prognostic factors for esophageal cancer (EC). Intraoperative molecular imaging (IMI) using tumor-targeted tracers is effective in many cancer types. However, there are no EC-specific IMI tracers. We sought to test a cathepsin activity-based tracer (VGT-309) for EC resection.</p><p><strong>Methods: </strong>Murine (AKR, HNM007) and human (OE19) EC cell lines were screened for cathepsin expression by western blotting. <i>In vitro</i> binding affinity of VGT-309 was evaluated by fluorescence microscopy. Flank tumor models were developed by injecting EC cells into the flanks of BALB/c or athymic nude mice. Mice pretreated with a cathepsin inhibitor (JPM-OEt) were used to confirm on target binding. Animals were injected with 2 mg/kg VGT-309, underwent IMI, and were sacrificed 24 hours after injection.</p><p><strong>Results: </strong>Cathepsins B, L, S, and X were expressed by EC cell lines, and all cell lines were labeled <i>in vitro</i> with VGT-309. Fluorescent signal was eliminated when cells were pretreated with JPM-OEt. On biodistribution analysis, VGT-309 accumulated in the liver, kidneys, and spleen without other organ involvement. VGT-309 selectively accumulated in flank allografts and xenografts, with mean signal-to-background ratio of 5.21 (IQR: 4.18-6.73) for flank allografts and 4.34 (IQR: 3.75-5.02) for flank xenografts. Fluorescence microscopy and histopathological analysis confirmed the selective accumulation of the tracer in tumors compared to background normal tissues.</p><p><strong>Conclusions: </strong>VGT-309 is an effective tracer for IMI of esophageal cancer. There is potential for clinical translation both as an adjunct to endoscopic detection and for complete removal of disease during esophagectomy.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"2022 ","pages":"5447290"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9451249","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}
引用次数: 4
Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. 线粒体代谢示踪剂F-AraG在健康志愿者中的生物分布[18F]。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2022-01-01 DOI: 10.1155/2022/3667417
Jelena Levi, Heying Duan, Shahriar Yaghoubi, Juliet Packiasamy, Lyna Huynh, Tina Lam, Faiq Shaikh, Deepak Behera, Hong Song, Joseph Blecha, Salma Jivan, Youngho Seo, Henry F VanBrocklin
{"title":"Biodistribution of a Mitochondrial Metabolic Tracer, [<sup>18</sup>F]F-AraG, in Healthy Volunteers.","authors":"Jelena Levi,&nbsp;Heying Duan,&nbsp;Shahriar Yaghoubi,&nbsp;Juliet Packiasamy,&nbsp;Lyna Huynh,&nbsp;Tina Lam,&nbsp;Faiq Shaikh,&nbsp;Deepak Behera,&nbsp;Hong Song,&nbsp;Joseph Blecha,&nbsp;Salma Jivan,&nbsp;Youngho Seo,&nbsp;Henry F VanBrocklin","doi":"10.1155/2022/3667417","DOIUrl":"https://doi.org/10.1155/2022/3667417","url":null,"abstract":"<p><strong>Purpose: </strong>[<sup>18</sup>F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [<sup>18</sup>F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry.</p><p><strong>Methods: </strong>Six healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study. Each subject received a bolus venous injection of [<sup>18</sup>F]F-AraG (dose range: 244.2-329.3 MBq) prior to four consecutive PET/MR whole-body scans. Blood samples were collected at regular intervals and vital signs monitored before and after tracer administration. Regions of interest were delineated for multiple organs, and the area under the time-activity curves was calculated for each organ and used to derive time-integrated activity coefficient (TIAC). TIACs were input for absorbed dose and effective dose calculations using OLINDA.</p><p><strong>Results: </strong>PET/MR examination was well tolerated, and no adverse effects to the administration of [<sup>18</sup>F]F-AraG were noted by the study participants. The biodistribution was generally reflective of the expression and activity profiles of the enzymes involved in [<sup>18</sup>F]F-AraG's cellular accumulation, mitochondrial kinase dGK, and SAMHD1. The highest uptake was observed in the kidneys and liver, while the brain, lung, bone marrow, and muscle showed low tracer uptake. The estimated effective dose for [<sup>18</sup>F]F-AraG was 0.0162 mSv/MBq (0.0167 mSv/MBq for females and 0.0157 mSv/MBq for males).</p><p><strong>Conclusion: </strong>Biodistribution of [<sup>18</sup>F]F-AraG in healthy volunteers was consistent with its association with mitochondrial metabolism. PET/MR [<sup>18</sup>F]F-AraG imaging was well tolerated, with a radiation dosimetry profile similar to other commonly used [<sup>18</sup>F]-labeled tracers. [<sup>18</sup>F]F-AraG's connection with mitochondrial biogenesis and favorable biodistribution characteristics make it an attractive tracer with a variety of potential applications.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"2022 ","pages":"3667417"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397147","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}
引用次数: 5
Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma. 颗粒酶B PET成像对肝细胞癌免疫检查点抑制剂反应的分层研究。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2021-12-09 eCollection Date: 2021-01-01 DOI: 10.1155/2021/9305277
Julian L Goggi, Boominathan Ramasamy, Yun Xuan Tan, Siddesh V Hartimath, Jun Rong Tang, Peter Cheng, Rasha Msallam, Ann-Marie Chacko, You Yi Hwang, Edward G Robins
{"title":"Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma.","authors":"Julian L Goggi,&nbsp;Boominathan Ramasamy,&nbsp;Yun Xuan Tan,&nbsp;Siddesh V Hartimath,&nbsp;Jun Rong Tang,&nbsp;Peter Cheng,&nbsp;Rasha Msallam,&nbsp;Ann-Marie Chacko,&nbsp;You Yi Hwang,&nbsp;Edward G Robins","doi":"10.1155/2021/9305277","DOIUrl":"https://doi.org/10.1155/2021/9305277","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a notoriously difficult cancer to treat. The recent development of immune checkpoint inhibitors has revolutionised HCC therapy; however, successful response is only observed in a small percentage of patients. Biomarkers typically used to predict treatment response in other tumour types are ineffective in HCC, which arises in an immune-suppressive environment. However, imaging markers that measure changes in tumour infiltrating immune cells may supply information that can be used to determine which patients are responding to therapy posttreatment. We have evaluated [<sup>18</sup>F]AlF-mNOTA-GZP, a radiolabeled peptide targeting granzyme B, to stratify response to ICIs in a HEPA 1-tumours, a syngeneic model of HCC. Posttherapy, <i>in vivo</i> tumour retention of [<sup>18</sup>F]AlF-mNOTA-GZP was correlated to changes in tumour volume and tumour-infiltrating immune cells. [<sup>18</sup>F]AlF-mNOTA-GZP successfully stratified response to immune checkpoint inhibition in the syngeneic HEPA 1-6 model. FACS indicated significant changes in the immune environment including a decrease in immune suppressive CD4+ T regulatory cells and increases in tumour-associated GZB+ NK+ cells, which correlated well with tumour radiopharmaceutical uptake. While the immune response to ICI therapies differs in HCC compared to many other cancers, [<sup>18</sup>F]AlF-mNOTA-GZP retention is able to stratify response to ICI therapy associated with tumour infiltrating GZB+ NK+ cells in this complex tumour microenvironment.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"9305277"},"PeriodicalIF":2.8,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40699909","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}
引用次数: 2
The Number of Frames on ECG-Gated 18F-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters. 心电图门控18F-FDG小动物PET帧数对左室收缩和舒张功能参数有显著影响。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2021-12-06 eCollection Date: 2021-01-01 DOI: 10.1155/2021/4629459
Christoph Eissler, Rudolf A Werner, Paula Arias-Loza, Naoko Nose, Xinyu Chen, Martin G Pomper, Steven P Rowe, Constantin Lapa, Andreas K Buck, Takahiro Higuchi
{"title":"The Number of Frames on ECG-Gated <sup>18</sup>F-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters.","authors":"Christoph Eissler,&nbsp;Rudolf A Werner,&nbsp;Paula Arias-Loza,&nbsp;Naoko Nose,&nbsp;Xinyu Chen,&nbsp;Martin G Pomper,&nbsp;Steven P Rowe,&nbsp;Constantin Lapa,&nbsp;Andreas K Buck,&nbsp;Takahiro Higuchi","doi":"10.1155/2021/4629459","DOIUrl":"https://doi.org/10.1155/2021/4629459","url":null,"abstract":"<p><strong>Objectives: </strong>This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats.</p><p><strong>Methods: </strong><sup>18</sup>F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed.</p><p><strong>Results: </strong>Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 ± 57.7 <i>μ</i>l<sup>∗</sup>, 380.8 ± 57.2 <i>μ</i>l<sup>∗</sup>, 398.0 ± 63.1 <i>μ</i>l<sup>∗</sup>, and 444.8 ± 75.3 <i>μ</i>l at 4, 8, 12, and 16 frames, respectively; <sup>∗</sup> <i>P</i> < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (<i>P</i> < 0.005), but not for 4, 8, and 12 frames.</p><p><strong>Conclusions: </strong>Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"4629459"},"PeriodicalIF":2.8,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39788143","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}
引用次数: 2
Comparison of 18F-FDG, 18F-Fluoroacetate, and 18F-FEPPA for Imaging Liver Fibrosis in a Bile Duct-Ligated Rat Model. 18F-FDG、18f -氟乙酸酯和18F-FEPPA在胆管结扎大鼠模型中肝纤维化成像的比较
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2021-11-27 eCollection Date: 2021-01-01 DOI: 10.1155/2021/7545284
Chun-Yi Wu, Hsin-Hua Hsieh, Pei-An Chu, Wen-Hsiang Hong, Ting-Yu Chang, Chia-Fang Hsu, Siao-Ting Lin, Po-Hsun Su, Shin-Lei Peng
{"title":"Comparison of <sup>18</sup>F-FDG, <sup>18</sup>F-Fluoroacetate, and <sup>18</sup>F-FEPPA for Imaging Liver Fibrosis in a Bile Duct-Ligated Rat Model.","authors":"Chun-Yi Wu,&nbsp;Hsin-Hua Hsieh,&nbsp;Pei-An Chu,&nbsp;Wen-Hsiang Hong,&nbsp;Ting-Yu Chang,&nbsp;Chia-Fang Hsu,&nbsp;Siao-Ting Lin,&nbsp;Po-Hsun Su,&nbsp;Shin-Lei Peng","doi":"10.1155/2021/7545284","DOIUrl":"https://doi.org/10.1155/2021/7545284","url":null,"abstract":"<p><p>Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with <sup>18</sup>F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [<sup>18</sup>F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([<sup>18</sup>F]FEPPA) (<i>n</i> = 3), [<sup>18</sup>F]fluoroacetate ([<sup>18</sup>F]FAc) (<i>n</i> = 3), and 18F-fluoro-2-deoxy-D-glucose ([<sup>18</sup>F]FDG) (<i>n</i> = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (<i>n</i> = 3), 1 (<i>n</i> = 3), 2 (<i>n</i> = 3), and 3 (<i>n</i> = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [<sup>18</sup>F]FEPPA and [<sup>18</sup>F]FDG, there was a significantly higher uptake in the liver after BDL (both <i>P</i> < 0.05), which lasted until week 2. However, the uptake of [<sup>18</sup>F]FAc in the liver was not significantly different before and after BDL (<i>P</i> = 0.28). Collectively, both [<sup>18</sup>F]FEPPA and [<sup>18</sup>F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [<sup>18</sup>F]FAc is not recommended to diagnose liver fibrosis.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":" ","pages":"7545284"},"PeriodicalIF":2.8,"publicationDate":"2021-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39834411","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}
引用次数: 2
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