EJNMMI Research最新文献

{"title":"Non-invasive arterial input function estimation using an MRA atlas and machine learning.","authors":"Rajat Vashistha, Hamed Moradi, Amanda Hammond, Kieran O'Brien, Axel Rominger, Hasan Sari, Kuangyu Shi, Viktor Vegh, David Reutens","doi":"10.1186/s13550-025-01253-3","DOIUrl":"10.1186/s13550-025-01253-3","url":null,"abstract":"<p><strong>Background: </strong>Quantifying biological parameters of interest through dynamic positron emission tomography (PET) requires an arterial input function (AIF) conventionally obtained from arterial blood samples. The AIF can also be non-invasively estimated from blood pools in PET images, often identified using co-registered MRI images. Deploying methods without blood sampling or the use of MRI generally requires total body PET systems with a long axial field-of-view (LAFOV) that includes a large cardiovascular blood pool. However, the number of such systems in clinical use is currently much smaller than that of short axial field-of-view (SAFOV) scanners. We propose a data-driven approach for AIF estimation for SAFOV PET scanners, which is non-invasive and does not require MRI or blood sampling using brain PET scans. The proposed method was validated using dynamic ¹⁸F-fluorodeoxyglucose [¹⁸F]FDG total body PET data from 10 subjects. A variational inference-based machine learning approach was employed to correct for peak activity. The prior was estimated using a probabilistic vascular MRI atlas, registered to each subject's PET image to identify cerebral arteries in the brain.</p><p><strong>Results: </strong>The estimated AIF using brain PET images (IDIF-Brain) was compared to that obtained using data from the descending aorta of the heart (IDIF-DA). Kinetic rate constants (K₁, k₂, k₃) and net radiotracer influx (K_i) for both cases were computed and compared. Qualitatively, the shape of IDIF-Brain matched that of IDIF-DA, capturing information on both the peak and tail of the AIF. The area under the curve (AUC) of IDIF-Brain and IDIF-DA were similar, with an average relative error of 9%. The mean Pearson correlations between kinetic parameters (K₁, k₂, k₃) estimated with IDIF-DA and IDIF-Brain for each voxel were between 0.92 and 0.99 in all subjects, and for K_i, it was above 0.97.</p><p><strong>Conclusion: </strong>This study introduces a new approach for AIF estimation in dynamic PET using brain PET images, a probabilistic vascular atlas, and machine learning techniques. The findings demonstrate the feasibility of non-invasive and subject-specific AIF estimation for SAFOV scanners.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"58"},"PeriodicalIF":3.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127022","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":"Radiation dosimetry of [¹¹C]TZ1964B as determined by whole-body PET imaging of nonhuman primates.","authors":"Baijayanta Maiti, Noah L Goldman, Mahdjoub Hamdi, Jason Lenox-Krug, Morvarid Karimi, Stephen M Moerlein, Richard Laforest, Tianyu Huang, Zhude Tu, Joel S Perlmutter, Scott A Norris","doi":"10.1186/s13550-025-01221-x","DOIUrl":"https://doi.org/10.1186/s13550-025-01221-x","url":null,"abstract":"<p><strong>Background: </strong>Phosphodiesterase 10A (PDE10A) is a postsynaptic, membrane bound cyclic nucleotide phosphodiesterase that is highly enriched in the striatal medium spiny neurons and regulates dopaminergic neurotransmission. The objective of this study is to determine the absorbed radiation dosimetry of a novel radiotracer for PDE10A: 3-(Methoxy-¹¹C)-2-((4-(1-methyl-4-(pyridine-4yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinolone ([¹¹C]TZ1964B) based on whole body PET imaging in nonhuman primates, a critical step before translating this radiotracer to imaging studies in humans. [¹¹C]TZ1964B may contribute to the clinical investigation of multiple neuropsychiatric conditions including Parkinson disease, Huntington disease and schizophrenia. For absorbed radiation measures, two males and one female cynomolgus monkeys (Macaca fascicularis) had intravenous injections of 302.3-384.4 MBq of [¹¹C]TZ1964B followed by sequential whole body PET imaging in a MicroPET-Focus220 scanner. Volumes of interest (VOIs) that either encompassed the entire organ or sampled regions of highest activity within larger organs were defined. Time-activity curves were derived from the PET data for each VOI, and analytical integration of its multi-exponential fit yielded the organ time-integrated activity. We generated human radiation dose estimates based on the scaled organ residence using OLINDA/EXM2.2.</p><p><strong>Results: </strong>Highest retention was observed in the liver with total time-integrated activity of ~ 0.23 h. Absorbed organ dosimetry was highest in the liver (53.3 μGy/MBq), making it the critical organ. Gallbladder (35.9 μGy/MBq) and spleen (35.4 μGy/MBq) were the next highest organs for absorbed radiation dose. Effective doses were estimated to be 5.02 and 5.84 μSv/MBq for males and females, respectively.</p><p><strong>Conclusions: </strong>This nonhuman primate dosimetry study suggests intravenous doses up to 938 MBq of [¹¹C]TZ1964B can be safely administered to human subjects for PET measurements of PDE10A activity. The tracer kinetic data is consistent with a hepatobiliary clearance pathway for the radiotracer.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"57"},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076814","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":"Test-retest repeatability of quantitative organ and tissue uptake using 20-minute dynamic multiparametric whole-body [¹⁸F]FDG PET/CT in patients with type 2 diabetes.","authors":"Jonathan M Baier, Kristian L Funck, Anna Dons-Jensen, Ole L Munk, Lars P Tolbod, Esben Laugesen, Per L Poulsen, Lars C Gormsen, André H Dias","doi":"10.1186/s13550-025-01249-z","DOIUrl":"10.1186/s13550-025-01249-z","url":null,"abstract":"<p><strong>Background: </strong>Recently developed dynamic whole-body PET/CT (D-WB PET/CT) protocols allow for measurements of potentially more precise metabolic parameters than the commonly used semiquantitative SUV. Most notable is the metabolic rate of FDG uptake (MR_FDG), which reflects quantitative glucose uptake into tissues and organs. However, data on the reproducibility of MR_FDG measurements are scarce, particularly in patients with perturbed glucose homeostasis such as type 2 diabetes. We therefore aimed to evaluate the test-retest repeatability of both MR_FDG and SUV in these patients.</p><p><strong>Results: </strong>Fifteen participants (mean age 71 ± 7 years; 2 females) with type 2 diabetes underwent a short 20-minute [¹⁸F]FDG D-WB PET/CT after 6 h fasting on two consecutive days. Both SUV and MR_FDG images were reconstructed from D-WB PET/CT data obtained 60-80 min post-injection of [¹⁸F]FDG. MR_FDG and SUV data were measured in organs and tissues, and repeatability was assessed with Bland-Altman analysis, intraclass correlation coefficients (ICC), repeatability coefficients (RPC) and coefficients of variation (wCV). There was high repeatability of both SUV_mean and MR_FDG-mean in all measured organs (ICC range: 0.65-0.95 for SUV_mean and 0.66-0.94 for MR_FDG-mean). SUV_mean generally demonstrated higher reliability (ICC) and lower variability (%RPC and %wCV) when compared to MR_FDG-mean. However, MR_FDG test-retest variation was < 19% in most analysed tissues, demonstrating that MR_FDG may be used as a precise marker of treatment response.</p><p><strong>Conclusion: </strong>This study demonstrates that MR_FDG calculated from D-WB PET/CT exhibit high repeatability, comparable to SUVs across most organs in patients with type 2 diabetes.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"56"},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983483","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":"Deep learning for Parkinson's disease classification using multimodal and multi-sequences PET/MR images.","authors":"Yan Chang, Jiajin Liu, Shuwei Sun, Tong Chen, Ruimin Wang","doi":"10.1186/s13550-025-01245-3","DOIUrl":"https://doi.org/10.1186/s13550-025-01245-3","url":null,"abstract":"<p><strong>Background: </strong>We aimed to use deep learning (DL) techniques to accurately differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), which share similar clinical presentations. In this retrospective analysis, 206 patients who underwent PET/MR imaging at the Chinese PLA General Hospital were included, having been clinically diagnosed with either PD or MSA; an additional 38 healthy volunteers served as normal controls (NC). All subjects were randomly assigned to the training and test sets at a ratio of 7:3. The input to the model consists of 10 two-dimensional (2D) slices in axial, coronal, and sagittal planes from multi-modal images. A modified Residual Block Network with 18 layers (ResNet18) was trained with different modal images, to classify PD, MSA, and NC. A four-fold cross-validation method was applied in the training set. Performance evaluations included accuracy, precision, recall, F1 score, Receiver operating characteristic (ROC), and area under the ROC curve (AUC).</p><p><strong>Results: </strong>Six single-modal models and seven multi-modal models were trained and tested. The PET models outperformed MRI models. The ¹¹C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (¹¹C-CFT) -Apparent Diffusion Coefficient (ADC) model showed the best classification, which resulted in 0.97 accuracy, 0.93 precision, 0.95 recall, 0.92 F1, and 0.96 AUC. In the test set, the accuracy, precision, recall, and F1 score of the CFT-ADC model were 0.70, 0.73, 0.93, and 0.82, respectively.</p><p><strong>Conclusions: </strong>The proposed DL method shows potential as a high-performance assisting tool for the accurate diagnosis of PD and MSA. A multi-modal and multi-sequence model could further enhance the ability to classify PD.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"55"},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978613","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":"PSMA-expressing, fluciclovine-negative vertebral hemangioma.","authors":"Azadeh Eslambolchi, Amin Haghighat Jahromi","doi":"10.1186/s13550-025-01248-0","DOIUrl":"https://doi.org/10.1186/s13550-025-01248-0","url":null,"abstract":"<p><strong>Background: </strong>False-positive findings in Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography (PSMA PET-CT) can complicate accurate staging of prostate cancer, especially in cases such as vertebral hemangiomas, a benign lesion of the spinal column. These ambiguities may result in unnecessary biopsies in patients with prostate cancer when PSMA PET findings are inconclusive.</p><p><strong>Case presentation: </strong>We present the case of a 68-year-old male with prostate cancer who had a PSMA-expressing, fluciclovine-negative vertebral hemangioma.</p><p><strong>Conclusion: </strong>This case highlights the role of fluciclovine PET-CT in distinguishing benign vertebral hemangiomas from prostate cancer metastases, improving diagnostic accuracy specifically in positive cases of PSMA PET-CT.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"54"},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973180","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":"Quantitative 177Lu-DOTATATE SPECT/CT is predictive of 6-month PRRT morphological response in midgut neuroendocrine tumors: a pilot study.","authors":"Iness Megherbi, Christopher Hoog, Marine Perrier, Hedia Brixi, Guillaume Cadiot, Christine Hoeffel-Fornes, David Morland","doi":"10.1186/s13550-025-01250-6","DOIUrl":"https://doi.org/10.1186/s13550-025-01250-6","url":null,"abstract":"<p><strong>Background: </strong>peptide receptor radionuclide therapy with 177Lu-DOTATATE has become an established second-line treatment for patients with advanced small intestine neuroendocrine tumors (siNET). Treatment efficacy is assessed several months after the end of treatment and is based on RECIST criteria. Post-therapy scintigraphy (PTS) can be performed after each cycle, but its value in early response assessment is debated particularly given the lack of quantification available in clinical routine. New quantification modules are now available, enabling automatic SUV calculation. The main goal of this study is to assess the value of the evolution of SUV between the first (C1) and the second (C2) cycle on quantitative PTS in predicting response to treatment. All patients with siNET referred to our center for treatment with 177Lu-DOTATATE were included. The SUVmax of the lesion with the greatest uptake was measured on PTS SPECT/CT at C1 and C2. ∆SUVmax was calculated. Linear regression between ∆SUVmax and 6-month RECIST percentage was used. Relative changes in tumor metabolic volume (MTV) were also studied along with clinical parameters.</p><p><strong>Results: </strong>twelve consecutive patients with progressive metastatic siNET were included. One patient showed partial response at 6 months, the other were considered as stable disease. Linear regression showed that 6-month RECIST percentage and ∆SUVmax were strongly correlated with the following regression formula: 6-month RECIST = -0.05 + 0.36 x ∆SUVmax (p < 0.001). ∆MTV was not predictive of response.</p><p><strong>Conclusion: </strong>we report a significant link between PTS ∆SUVmax and 6-month RECIST percentage in patients with siNET. Quantitative imaging would thus enable the prediction of 6-month response of 177Lu-DOTATATE as early as C2. These results need to be confirmed on a larger population.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"53"},"PeriodicalIF":3.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062863","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 heterodimeric radioligand labeled with gallium-68 targeting fibroblast activation protein.","authors":"Chengde Xie, Lei Peng, Hui Nie, Tianhong Yang, Renbo Wu, Dake Zhang, Fuhua Wen, Junyu Chen, Lingyu Xue, Xiangsong Zhang, Zhihao Zha, Jianjun Wang","doi":"10.1186/s13550-025-01230-w","DOIUrl":"https://doi.org/10.1186/s13550-025-01230-w","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast activation protein (FAP) targeting radiotracers have emerged as promising agents for cancer imaging and therapy. Recent advancements have focused on optimizing these agents for better tumor targeting and enhanced theranostic efficacy. In this study, we introduced a novel heterodimeric radioligand labeled with gallium-68, which targets FAP. We aimed to evaluate its in vitro and in vivo performance, comparing its efficacy with monomeric FAPI derivatives.</p><p><strong>Results: </strong>The heterodimeric ligand BiFAPI was synthesized by conjugating a cyclic peptide with a quinoline-based motif via a DOTA chelator. [⁶⁸ Ga]Ga-BiFAPI demonstrated high radiochemical purity (> 95%) and exceptional stability in physiological conditions, as well as in both PBS and serum. In vitro studies revealed that the binding affinity of BiFAPI was comparable to that of FAP2286 and FAPI-04. Notably, [⁶⁸ Ga]Ga-BiFAPI exhibited superior cellular uptake, with rapid internalization and slower efflux rates. Micro-PET/CT imaging in tumor-bearing mice demonstrated significantly higher tumor uptake than [⁶⁸ Ga]Ga-FAP2286 and [⁶⁸ Ga]Ga-FAPI-04. Co-injection with a FAP inhibitor reduced tumor uptake, confirming the tracer's FAP specificity. In vitro autoradiography, immunohistochemistry, and Western blotting confirmed the correlation between radioactive tracer accumulation and FAP-positive regions. Biodistribution studies revealed high tumor-to-blood ratios and rapid clearance from non-target tissues, further supporting the tracer's favorable pharmacokinetics.</p><p><strong>Conclusion: </strong>[⁶⁸ Ga]Ga-BiFAPI demonstrated superior tumor-targeting properties, higher tumor uptake, and favorable pharmacokinetics compared to [⁶⁸ Ga]Ga-FAP2286 and [⁶⁸ Ga]Ga-FAPI-04. Its promising performance in preclinical models positioned it as a potentially valuable agent for FAP-targeted PET imaging and cancer theranostics.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"52"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968301","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":"Whole-body and site specific [¹⁸F]FDG uptake patterns on PET/CT have limited value in differentiating between polymyalgia rheumatica and other inflammatory diseases: two cohorts of treatment-naïve suspected polymyalgia rheumatica.","authors":"Andreas Wiggers Nielsen, Gijs D van Praagh, Kornelis S M van der Geest, Ib Tønder Hansen, Berit Dalsgaard Nielsen, Søren Geill Kjær, Jesper Blegvad-Nissen, Kate Rewers, Christian Møller Sørensen, Elisabeth Brouwer, Ellen-Margrethe Hauge, Lars Christian Gormsen, Riemer H J A Slart, Kresten Krarup Keller","doi":"10.1186/s13550-025-01233-7","DOIUrl":"https://doi.org/10.1186/s13550-025-01233-7","url":null,"abstract":"<p><strong>Background: </strong>It has been hypothesized that 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) computed tomography (CT) can distinguish polymyalgia rheumatica (PMR) from non-PMR patients based on the [¹⁸F]FDG-uptake patterns. Nevertheless, a comprehensive assessment of whole-body [¹⁸F]FDG-patterns across all uptaking musculoskeletal sites, as well as site-specific [¹⁸F]FDG-uptake patterns, has not been conducted. Therefore, this study aimed to investigate both the overall whole-body [¹⁸F]FDG-uptake patterns and the specific uptake patterns at individual sites in patients suspected of having PMR.</p><p><strong>Methods: </strong>Two distinct cohorts of patients with suspected PMR from Denmark and the Netherlands were prospectively included, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts consisted of treatment-naïve patients, who underwent pre-treatment [¹⁸F]FDG-PET/CT scans. The [¹⁸F]FDG-uptake was then assessed across 34 different anatomical sites. Furthermore, the site-specific [¹⁸F]FDG-uptake pattern within each anatomical site was categorized according to its shape.</p><p><strong>Results: </strong>Patients with PMR were more likely than non-PMR patients to have bilateral [¹⁸F]FDG-uptake equal to or above liver compared at the ischial tuberosities (91%/41%), shoulder joints (86%/45%), hip joints (83%/52%), and along the lumbar spinal processes (70%/30%). However, a subgroup analysis comparing non-PMR patients with other inflammatory conditions to patients with PMR revealed that several non-PMR patients exhibited a similar whole-body [¹⁸F]FDG-uptake pattern. Furthermore, site-specific [¹⁸F]FDG-uptake patterns were similar in patients with PMR and non-PMR.</p><p><strong>Conclusion: </strong>Assessing whole-body or site-specific [¹⁸F]FDG-uptake patterns does not improve the diagnostic accuracy in distinguishing PMR from other inflammatory diseases. Consequently, [¹⁸F]FDG-PET/CT should mainly be used to rule out a clinical diagnosis of PMR.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"51"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996918","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 a simplified radiolabeling method for a PARP inhibitor in an animal model of breast cancer.","authors":"Chi-Chang Weng, Chao-Chih Chiang, Yi-Hsiu Chung, Yi-Pei Ho, Yu-Chuan Chang, Ing-Tsung Hsiao, Robert H Mach","doi":"10.1186/s13550-025-01236-4","DOIUrl":"https://doi.org/10.1186/s13550-025-01236-4","url":null,"abstract":"<p><strong>Background: </strong>Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors were recently approved by the US Food and Drug Administration for use in cancer treatment. To facilitate the discovery of novel PARP-targeting ligands, a radioiodinated ligand, I-125-KX1, was developed and validated for its specificity to PARP-1; however, its preparation procedure is time-consuming. The present study employed a solid-phase extraction (SPE) method in the radiolabeling procedure of I-123/125-KX1 and evaluated its binding specificity by using receptor binding assays, autoradiography, and in vivo single photon emission computed tomography (SPECT) imaging technique.</p><p><strong>Results: </strong>Through the incorporation of the SPE purification method as the final step in the radioiodination procedure, the resultant product I-123/125-KX1 exhibited high radiochemical purity (> 99%) and an acceptable radiochemical yield (58.6% for I-123-KX1, 73.3% for I-125-KX1). The binding characteristics of this radiotracer were validated through saturation binding assays conducted on MDA-MB-231 and MCF-7 cells. The K_d values obtained for the tracer (~ 1.0 nM) was consistent with values reported in the literature, and the B_max values of these two cell lines (2017 ± 178 fmol/mg on MDA-MB-231 vs. 1393 ± 105 fmol/mg on MCF-7) were in line with the results from Western blot analyses. To demonstrate the in vivo imaging ability of I-123-KX1 prepared in this study, an MDA-MB-231 tumor animal model was used and the tracer displayed a suitable uptake on the tumor tissues (6.9 ± 0.8%ID/mL). The binding specificity of the SPE-purified I-125-KX1 was further verified using in vitro autoradiography in conjunction with various PARP inhibitors. Additionally, an anti-PARP-1 immunohistochemistry experiment was conducted, which revealed that the autoradiograms of the radiotracer displayed a similar pattern.</p><p><strong>Conclusions: </strong>This suggests that the I-123/125-KX1 prepared using the SPE method showed some comparable properties to those from the traditional method, indicating its potential suitability for future radioligand preparation in PARP studies. However, further characterization studies may be needed to confirm its efficacy.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"50"},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970366","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":"Spatial distribution of fractionally administered holmium microspheres in non-tumorous human liver tissue: how livers survive transarterial radioembolisation.","authors":"Anne van den Brekel, Tess J Snoeijink, Vincent E de Meijer, Milou Boswinkel, Koert P de Jong, Joey Roosen, Alexandra G Arranja, Jurgen J Fütterer, Simeon J S Ruiter, J Frank W Nijsen","doi":"10.1186/s13550-025-01240-8","DOIUrl":"https://doi.org/10.1186/s13550-025-01240-8","url":null,"abstract":"<p><strong>Background: </strong>Relatively high mean absorbed doses to the non-tumorous liver tissue (NTLT) are generally well tolerated in transarterial radioembolisation (TARE), potentially due to a heterogeneous dose distribution. This study investigates the macroscopic and microscopic distribution of fractionally administered TARE holmium microspheres in NTLT using an experimental setup of ex vivo perfused human donor livers under magnetic resonance imaging (MRI), and validates these findings through a comparison with MRI data from TARE-treated patients.</p><p><strong>Results: </strong>MRI-based dose maps of the TARE-treated ex vivo livers and patients revealed a heterogeneous dose distribution pattern throughout the NTLT (heterogeneity index (HI) range 2.96-10.11). Microscopic analysis confirmed this, as a wide variation in the percentage of tissue within 2.1 mm of microspheres (5.4%-84.3%) was observed. Microspheres administered in consecutive fractions decreased the heterogeneity, which was observed macroscopically by a decreased HI, and microscopically by the formation of new microsphere clusters. However, this HI decrease appeared finite, and new clusters formed near existing clusters, maintaining the overall distribution pattern.</p><p><strong>Conclusions: </strong>TARE induces a heterogeneous dose distribution pattern in human NTLT. This heterogeneous dose distribution pattern persists across additional microsphere fractions, leaving parts of the NTLT unexposed to lethal doses of ionising radiation. Combined with the regenerative capacity of the liver, this may explain why relatively high mean absorbed doses to the NTLT are generally well tolerated in TARE.</p><p><strong>Registration: </strong>For validation purposes, clinical data from patients who participated in a previous study (ClinicalTrials.gov, identifier NCT04269499, registered on February 13, 2020) was analysed in the current study.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"49"},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983637","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}