EJNMMI Research最新文献

{"title":"Preclinical evaluation of [¹⁸F]SYN1 and [¹⁸F]SYN2, novel radiotracers for PET myocardial perfusion imaging.","authors":"Seweryn Krajewski, Lukasz Steczek, Karina Gotowicz, Urszula Karczmarczyk, Joanna Towpik, Ewa Witkowska-Patena, Krzysztof Łyczko, Maciej Mazur, Przemysław Kozanecki, Joanna Włostowska, Juhani Knuuti, Mirosław Dziuk, Piotr Garnuszek, Cezary Kozanecki","doi":"10.1186/s13550-024-01122-5","DOIUrl":"10.1186/s13550-024-01122-5","url":null,"abstract":"<p><strong>Background: </strong>Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the ¹⁸F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [¹⁸F]SYN1 and [¹⁸F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.</p><p><strong>Results: </strong>The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [¹⁸F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [¹⁸F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [¹⁸F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [¹⁸F]SYN1 and 0.0109 mSv/MBq for [¹⁸F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [¹⁸F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M₁ and M₂ receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.</p><p><strong>Conclusion: </strong>[¹⁸F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [¹⁸F]SYN2 in clinical studies.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasensitive detection of uveal melanoma using [¹⁸F]AlF-NOTA-PRGD2 PET imaging.","authors":"Ling Wang, Xue Zhu, Yan Xue, Zhihong Huang, Wenjun Zou, Zhengwei Zhang, Mengxi Yu, Donghui Pan, Ke Wang","doi":"10.1186/s13550-024-01123-4","DOIUrl":"10.1186/s13550-024-01123-4","url":null,"abstract":"<p><strong>Background: </strong>Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [¹⁸F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [¹⁸F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [¹⁸F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [¹⁸F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [¹⁸F]AlF-NOTA-PRGD2 and ¹⁸F-labelled fluorodeoxyglucose ([¹⁸F]FDG) PET imaging in UM xenografts and UM patients were conducted.</p><p><strong>Results: </strong>The in vitro data showed that [¹⁸F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [¹⁸F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [¹⁸F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [¹⁸F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [¹⁸F]FDG tracer.</p><p><strong>Conclusion: </strong>[¹⁸F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [¹⁸F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [¹⁸F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical value of ⁶⁸Ga-pentixafor PET/CT in patients with primary aldosteronism and bilateral lesions: preliminary results of a single-centre study.","authors":"Rui Zuo, Shuang Liu, Wenbo Li, Zhu Xia, Lu Xu, Hua Pang","doi":"10.1186/s13550-024-01125-2","DOIUrl":"10.1186/s13550-024-01125-2","url":null,"abstract":"<p><strong>Background: </strong>Subtype diagnosis of primary aldosteronism (PA) is used to determine treatment, and the potential utility of ⁶⁸Ga-pentixafor PET/CT for investigation of PA has long been recognized. The study aimed to evaluate the clinical value of ⁶⁸Ga-pentixafor PET/CT in the diagnosis and prognosis of patients with bilateral lesions identified by CT.</p><p><strong>Methods: </strong>In total, 25 patients with PA and bilateral lesions on CT were retrospectively evaluated. All patients underwent ⁶⁸Ga-Pentixafor PET/CT and adrenal vein sampling. The analysis focused on establishing the relationship between bilateral adrenal lesions SUVmax and the ratio of bilateral adrenal lesions SUVmax (CON) and clinical diagnosis, treatment outcomes, and KCNJ5 gene status.</p><p><strong>Results: </strong>The concordance rate between ⁶⁸Ga-Pentixafor PET/CT and adrenal venous sampling was 65.2% (15/23). The lateralization results of ⁶⁸Ga-pentixafor PET/CT supported the clinical decisions of 20 patients with PA, 90% of whom showed effectiveness in treatment. The SUVmax on the dominant side of the surgically treated patients was higher than that of patients treated with drugs. The SUVmax of the KCNJ5 mutant group was higher than that of the KCNJ5 wild group, and ⁶⁸Ga-Pentixafor uptake was correlated with KCNJ5 gene status.</p><p><strong>Conclusions: </strong>⁶⁸Ga-Pentixafor PET/CT proves beneficial for patients with PA with bilateral lesions on CT. The treatment is generally effective based on the results of PET lateralization. Simultaneously, a certain relationship exists between ⁶⁸Ga-Pentixafor PET/CT and KCNJ5 gene status, warranting further analysis.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respective contribution of baseline clinical data, tumour metabolism and tumour blood-flow in predicting pCR after neoadjuvant chemotherapy in HER2 and Triple Negative breast cancer.","authors":"Neree Payan, Benoit Presles, Charles Coutant, Isabelle Desmoulins, Sylvain Ladoire, Françoise Beltjens, François Brunotte, Jean-Marc Vrigneaud, Alexandre Cochet","doi":"10.1186/s13550-024-01115-4","DOIUrl":"10.1186/s13550-024-01115-4","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC).</p><p><strong>Methods: </strong>One hundred and twenty-eight BC patients underwent a ¹⁸F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours.</p><p><strong>Results: </strong>In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value<0.01) higher than C models and better than C+M+BF models (mean balanced accuracy of 0.66, 0.61, and 0.64 respectively). For HER2 tumours, equal performances were noted for C and C+M models, with performances higher than C+M+BF models (mean balanced accuracy of 0.64, and 0.61 respectively). Regarding TN tumours, the best classification results were reported for C+M models, with better performances than C and C+M+BF models but not significantly (mean balanced accuracy of 0.65, 0.63, and 0.62 respectively).</p><p><strong>Conclusion: </strong>Baseline clinical data combined with global and texture tumour metabolism parameters assessed by ¹⁸F-FDG PET/CT provide a better prediction of pCR after NAC in patients with BC compared to clinical parameters alone for TN, and HER2 and TN tumours together. In contrast, adding BF parameters to the models did not improve prediction, regardless of the tumour subgroup analysed.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of [¹⁸F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson's disease: pharmacokinetic and efficacy analysis.","authors":"Jae Hun Ahn, Min Hwan Kim, Kyongkyu Lee, Keumrok Oh, Hyunwoo Lim, Hee Seup Kil, Soon Jeong Kwon, Jae Yong Choi, Dae Yoon Chi, Yong Jin Lee","doi":"10.1186/s13550-024-01121-6","DOIUrl":"10.1186/s13550-024-01121-6","url":null,"abstract":"<p><strong>Background: </strong>N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). ¹²³I- and ¹⁸F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [¹⁸F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [¹⁸F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [¹⁸F]FP-CIT and its efficacy for PD diagnosis using murine models.</p><p><strong>Results: </strong>Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [¹⁸F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [¹⁸F]FP-CIT injection. [¹⁸F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [¹⁸F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [¹⁸F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011).</p><p><strong>Conclusions: </strong>This study fills the gap regarding insufficient preclinical studies on [¹⁸F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [¹⁸F]FP-CIT excretion, provide complementary evidence that [¹⁸F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective clinical study of the influence of oral protein intake on [¹⁸F]FET-PET uptake and test-retest repeatability in glioma.","authors":"Sarah Chehri, Otto Mølby Henriksen, Lisbeth Marner, Mette Christensen, Aida Muhic, Hans Skovgaard Poulsen, Ian Law","doi":"10.1186/s13550-024-01119-0","DOIUrl":"10.1186/s13550-024-01119-0","url":null,"abstract":"<p><strong>Background: </strong>O-(2-[¹⁸F]fluoroethyl)-L-tyrosine positron emission tomography ([¹⁸F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test-retest variation of [¹⁸F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [¹⁸F]FET-PET metrics and to assess the impact of protein-intake prior to [¹⁸F]FET PET scanning of gliomas.</p><p><strong>Results: </strong>Test-retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and - 0.13 (+ 9.7% and - 9.0%) for mean tumour-to-background ratio (TBR_mean), + 0.43 and - 0.28 (+ 19.6% and - 11.8%) for maximal tumour-to-background ratio (TBR_max), and + 2.14 cm³ and - 1.53 ml (+ 219.8% and - 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the L-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV - 25%) and in tumour (maximal SUV - 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBR_mean and TBR_max were only borderline significant, and changes generally within the variability observed in the group with no protein intake.</p><p><strong>Conclusion: </strong>The test-retest repeatability was found to be good, and better for TBR_max and TBR_mean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [¹⁸F]FET PET scan decreases uptake of [¹⁸F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnosis and staging of paraquat-induced pulmonary fibrosis using [¹⁸F]F-FAPI-42 PET/CT imaging.","authors":"Dimei Zhang, Yusheng Shi, Jiangwei Kong, Na Chen, Guiting Li, Mingfang Wang, Guoxia Zhang, Chuangyan Zhai","doi":"10.1186/s13550-024-01118-1","DOIUrl":"10.1186/s13550-024-01118-1","url":null,"abstract":"<p><strong>Background: </strong>Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [¹⁸F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis.</p><p><strong>Methods: </strong>After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [¹⁸F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [¹⁸F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUV_mean) was calculated.</p><p><strong>Results: </strong>PET signals revealed that in areas with evident lesions on CT, the SUV_mean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUV_mean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [¹⁸F]F-FAPI-42 binding to activated fibroblasts.</p><p><strong>Conclusion: </strong>[¹⁸F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of [¹¹C]UCB-A positron emission tomography in human brains.","authors":"Mengfei Xiong, Mark Lubberink, Lieuwe Appel, Xiaotian Tsong Fang, Torsten Danfors, Eva Kumlien, Gunnar Antoni","doi":"10.1186/s13550-024-01117-2","DOIUrl":"10.1186/s13550-024-01117-2","url":null,"abstract":"<p><strong>Background: </strong>In preclinical studies, the positron emission tomography (PET) imaging with [¹¹C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [¹¹C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.</p><p><strong>Results: </strong>Twelve healthy subjects underwent 90-min baseline [¹¹C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [¹¹C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [¹¹C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.</p><p><strong>Conclusions: </strong>[¹¹C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11183037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of gastrin-releasing peptide receptor, prostate-specific membrane antigen, and neurotensin receptor 1 as potential biomarkers for accurate prostate cancer stratified diagnosis.","authors":"Ling Xiao, Zhihui Fang, Yongxiang Tang, Yanyan Sun, Zehua Zhu, Jian Li, Ming Zhou, Nengan Yang, Kai Zheng, Shuo Hu","doi":"10.1186/s13550-024-01116-3","DOIUrl":"10.1186/s13550-024-01116-3","url":null,"abstract":"<p><strong>Background: </strong>Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging.</p><p><strong>Methods: </strong>In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (⁶⁸Ga-NOTA-RM26 and ⁶⁸Ga-NOTA-PSMA617) PET/CT.</p><p><strong>Results: </strong>In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of ⁶⁸Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of ⁶⁸Ga-NOTA-RM26 than those with high GS (P = 0.001).</p><p><strong>Conclusions: </strong>This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New improved radiometabolite analysis method for [¹⁸F]FTHA from human plasma: a test-retest study with postprandial and fasting state.","authors":"Richard Aarnio, Anna Kirjavainen, Johan Rajander, Sarita Forsback, Kari Kalliokoski, Pirjo Nuutila, Zvonko Milicevic, Tamer Coskun, Axel Haupt, Iina Laitinen, Merja Haaparanta-Solin","doi":"10.1186/s13550-024-01114-5","DOIUrl":"10.1186/s13550-024-01114-5","url":null,"abstract":"<p><strong>Background: </strong>Fatty acid uptake can be measured using PET and 14-(R,S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid ([¹⁸F]FTHA). However, the relatively rapid rate of [¹⁸F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [¹⁸F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [¹⁸F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [¹⁸F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [¹⁸F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.</p><p><strong>Results: </strong>The new TLC method separated seven [¹⁸F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [¹⁸F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [¹⁸F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.</p><p><strong>Conclusions: </strong>The newly developed improved radio-TLC method for [¹⁸F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [¹⁸F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [¹⁸F]FTHA metabolic rate under different study settings.</p><p><strong>Trial registration: </strong>EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05132335 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}