{"title":"Differentiation and correlation of regional uptake heterogeneity with cardiac dysfunction in biopsy-proven transthyretin amyloid cardiomyopathy using quantitative single-photon emission computed tomography/computed tomography: a single-center, cross-sectional study.","authors":"Masakazu Tsujimoto, Hideki Kawai, Shingo Tanahashi, Masayoshi Sarai, Yasuki Asada, Hideo Izawa","doi":"10.1186/s13550-025-01292-w","DOIUrl":"10.1186/s13550-025-01292-w","url":null,"abstract":"<p><strong>Background: </strong>Cardiac amyloidosis requires quantitative assessment using technetium-99m pyrophosphate (<sup>99m</sup>Tc-PYP) single-photon emission computed tomography (SPECT)/computed tomography (CT) for adequate discrimination and evaluation of disease extent. This study aimed to evaluate the utility of standardized uptake value (SUV) analysis using <sup>99m</sup>Tc-PYP SPECT/CT in pathologically-confirmed transthyretin amyloid cardiomyopathy (ATTR-CM). The study also explored the relationship between local uptake heterogeneity and indicators of cardiac impairment.</p><p><strong>Methods: </strong>Forty patients diagnosed via heart biopsy and genetic analysis (20 ATTR-CM; 4 light-chain amyloidosis, 16 non-amyloidosis) were enrolled. The mean SUVs of the heart and aorta were measured using SPECT images. Discrimination performance was evaluated by comparing each SUV, the heart-to-aorta ratio (rSUV<sub>H/Ao</sub>), and the heart-to-contralateral-lung ratio with pathological findings serving as the gold standard. Polar maps were analyzed to assess local SUV distribution in patients with ATTR-CM. The coefficient of variation (COV) of myocardial uptake, difference score between the septum and lateral wall (%DS), base-to-apex variability, and total cardiac SUV were calculated and compared with echocardiographic parameters.</p><p><strong>Results: </strong>All metrics were significantly different between the ATTR-CM and non-amyloidosis groups. The rSUV<sub>H/Ao</sub> effectively differentiated patients with ATTR-CM from those with light-chain or non-amyloidosis. Local myocardial SUV distribution correlated with impaired cardiac function. Notably, COV showed significant correlations with e' (R = 0.782) and E/e' (R = - 0.625), linking heterogeneity to myocardial stiffness and diastolic dysfunction. Larger %DS, which predominantly reflected the ATTR-CM pattern of high septal uptake, correlated significantly with thinner walls (average wall thickness, R = - 0.655; relative wall thickness, R = - 0.486). As the total cardiac SUV increased, the %DS decreased (reflecting more homogeneous distribution), and global longitudinal strain worsened (R = 0.614). These observations indicated that greater impairment was associated with a higher disease burden.</p><p><strong>Conclusions: </strong>This study demonstrated that quantitative SPECT analysis provides a valuable tool for the diagnostic evaluation and differentiation of ATTR-CM. The rSUV<sub>H/Ao</sub> offers high discriminatory performance. Local heterogeneity and total myocardial uptake are closely related to the disease burden and extent, as reflected by structural and functional abnormalities on echocardiography. These findings suggest potential relevance to the non-invasive assessment of these aspects of the disease at a single time point.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"97"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764780","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}
EJNMMI ResearchPub Date : 2025-08-01DOI: 10.1186/s13550-025-01302-x
Tyrillshall S T Damiana, Lilian van den Brink, Lisette W de Kreij-de Bruin, Debra C Stuurman, Corrina M A de Ridder, Simone U Dalm
{"title":"Chemotherapy alters radiosensitivity and GRPR expression of prostate and breast cancer cells.","authors":"Tyrillshall S T Damiana, Lilian van den Brink, Lisette W de Kreij-de Bruin, Debra C Stuurman, Corrina M A de Ridder, Simone U Dalm","doi":"10.1186/s13550-025-01302-x","DOIUrl":"10.1186/s13550-025-01302-x","url":null,"abstract":"<p><strong>Background: </strong>Gastrin releasing peptide receptor (GRPR)-targeting radiotracers have been studied (pre)-clinically with promising results. Patients eligible for this treatment are likely to have undergone prior treatments with other anti-cancer agents, including chemotherapy. Chemotherapies are known to alter cancer cell's gene expression and radiosensitivity, potentially impacting GRPR expression and the response to radionuclide therapy. We studied the effect of two commonly applied chemotherapies, doxorubicin (DXR) and docetaxel (DTX), on GRPR expression, GRPR radiotracer uptake, and response to external beam radiation therapy (EBRT) and targeted radionuclide treatment, in prostate cancer (PCa) and breast cancer (BC) cells. Additionally, in-vivo uptake of the GRPR-targeting radiotracer \"NeoB\" in PC-3 and T47D xenograft-bearing mice was assessed using SPECT/CT following chemotherapy treatment.</p><p><strong>Results: </strong>DTX significantly decreased GRPR expression, radiotracer uptake, and radiosensitivity of PC-3 cells in-vitro. DXR pre-treated T47D cells demonstrated an increased GRPR expression and radiotracer uptake, and were less sensitive to EBRT. In-vivo, DTX pre-treatment increased [<sup>177</sup>Lu]Lu-NeoB uptake in PC-3 xenografts, but this was not GRPR mediated. DXR pre-treatment did not alter [<sup>177</sup>Lu]Lu-NeoB uptake in T47D xenografts, but an increase in GRPR mRNA expression was observed.</p><p><strong>Conclusion: </strong>Our data demonstrated that chemotherapy alters mechanisms relevant for the success of GRPR-mediated radionuclide therapy in PCa and BC cells in-vitro. These finding were less prominent in-vivo and additional studies are needed to unravel this.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"98"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764779","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}
EJNMMI ResearchPub Date : 2025-07-31DOI: 10.1186/s13550-025-01291-x
Zhixin Sun, Jacqueline M Godbe, Alexander Zheleznyak, Brad Manion, Junhao Hu, Julie L Prior, Kathleen Duncan, Ulugbek S Kamilov, Monica Shokeen
{"title":"Advanced quantification pipeline reveals new spatial and temporal tumor characteristics in preclinical multiple myeloma.","authors":"Zhixin Sun, Jacqueline M Godbe, Alexander Zheleznyak, Brad Manion, Junhao Hu, Julie L Prior, Kathleen Duncan, Ulugbek S Kamilov, Monica Shokeen","doi":"10.1186/s13550-025-01291-x","DOIUrl":"10.1186/s13550-025-01291-x","url":null,"abstract":"<p><strong>Background: </strong>Radiological imaging plays an indispensable role in both preclinical and clinical studies of multiple myeloma (MM). However, manual quantification in longitudinal small animal PET/CT is limited by annotator bias, signal artifacts from urinary/fecal excretion, and voxel misalignment due to non-rigid registration. To address these challenges and improve characterization of tumor biology, we developed a semi-automated PET/CT quantification pipeline targeting defined regions of interest (ROIs) within the bone marrow-rich mouse skeleton, achieving sub-organ spatial resolution, including in anatomically complex sites such as the pelvis. We applied this MM-specific preclinical pipeline to analyze tumor distribution in a longitudinal molecular PET study using an immunocompetent mouse model of skeletally disseminated MM. An Attention U-Net was trained to segment the thoracolumbar spine, pelvis and pelvic joints, sacrum, and femurs from 2D CT slices. A custom algorithm masked spillover signal from physiological excretion, and a PCA-based projection was used to map tumor distribution along the skeletal axis. Quantification metrics included mean and maximum standardized uptake values (SUV<sub>mean</sub>, SUV<sub>max</sub>) from PET and Hounsfield Units (HU) from CT to assess tumor burden, spatiotemporal tumor distribution, and bone involvement.</p><p><strong>Results: </strong>Tumor burden localized preferentially to skeletal regions near joints. Using precise CT-based alignment (DICE = 0.966 ± 0.005), we detected early disease progression and aggressive phenotypes. A marked increase in tumor uptake was observed by day 18 post-implantation, with significant SUV<sub>mean</sub> increases in the spine (p = 0.012), left/right femurs (p = 0.007/0.006), pelvis and pelvic joints (p = 0.018), and sacrum (p = 0.02). Notably, sex-based differences were identified: female mice showed greater bone loss near the hip joint at later stages, with significant HU<sub>mean</sub> reductions at days 25 (p = 0.008) and 32 (p = 0.002).</p><p><strong>Conclusions: </strong>This pipeline enables reproducible, anatomically precise quantification of region-specific trends in MM progression, including joint-specific lesion tropism and sex-based differences, from longitudinal PET/CT scans. By mitigating common challenges such as excretion artifacts and inconsistent mouse positioning, our approach overcomes limitations of manual analysis and enhances evaluation of tumor biology and treatment response in preclinical models of bone-involved cancers.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"95"},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752702","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":"Neuropathological correlations of <sup>18</sup>F-florzolotau PET in a case with pick's disease.","authors":"Hisaomi Suzuki, Manabu Kubota, Shin Kurose, Kenji Tagai, Hironobu Endo, Mitsumoto Onaya, Yasuharu Yamamoto, Naruhiko Sahara, Masahiro Ohgidani, Chie Haga, Hiroya Hara, Haruhiko Akiyama, Keisuke Takahata, Makoto Higuchi","doi":"10.1186/s13550-025-01296-6","DOIUrl":"10.1186/s13550-025-01296-6","url":null,"abstract":"<p><strong>Background: </strong>Pick's disease (PiD) is classified as frontotemporal lobar degeneration with pathological tau aggregates. Positron emission tomography (PET) with <sup>18</sup>F-florzolotau provides high-contrast imaging of diverse tau fibrils. While our previous work demonstrated the detectability of three repeat (3R) tau pathology by <sup>18</sup>F-florzolotau PET in an autopsy-confirmed PiD patient, its potential for quantitative assessment of 3R tau aggregates in living individuals remains unclear. In this study, we analyzed correlations between in vivo <sup>18</sup>F-florzolotau retentions and postmortem neuropathological data across brain regions in the same case with PiD.</p><p><strong>Case presentation: </strong>The patient was 60 years of age at the time of death and had been diagnosed with behavioral variant frontotemporal dementia. The patient underwent <sup>18</sup>F-florzolotau PET one year prior to death and was given the pathological diagnosis of PiD by brain autopsy. Regional tau pathology was assessed using Bodian's silver staining and immunohistochemistry with a monoclonal antibody (AT8). Histopathological assays revealed abundant intraneuronal Pick bodies along with neuropil threads in frontotemporal and other brain areas. In the cerebral cortex, AT8-positive areas exhibited a significant positive correlation with <sup>18</sup>F-florzolotau binding in the corresponding regions (Pearson's r = 0.81, p < 0.001) estimated as standardized uptake value ratio corrected for partial volume effect. In contrast, no such associations were found in subcortical structures. Furthermore, a substantial proportion of Pick bodies displayed fluorescence co-labelled with florzolotau and AT8 antibodies.</p><p><strong>Conclusions: </strong>Collectively, the present findings support the capability of <sup>18</sup>F-florzolotau PET for the in vivo quantification of 3R tau fibrils.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"96"},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759380","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}
EJNMMI ResearchPub Date : 2025-07-29DOI: 10.1186/s13550-025-01289-5
Feredun Azari, Gregory T Kennedy, Ian Folkert, Gregory Jones, Ashley Chang, Andrew Conner, Elizabeth Bernstein, Bilal Nadeem, Neil T Sullivan, Evgeniy Eruslanov, Steven Albelda, Philip Low, Sunil Singhal
{"title":"A fibroblast activation protein targeted optical tracer for identifying primary and metastatic sarcoma during resection.","authors":"Feredun Azari, Gregory T Kennedy, Ian Folkert, Gregory Jones, Ashley Chang, Andrew Conner, Elizabeth Bernstein, Bilal Nadeem, Neil T Sullivan, Evgeniy Eruslanov, Steven Albelda, Philip Low, Sunil Singhal","doi":"10.1186/s13550-025-01289-5","DOIUrl":"10.1186/s13550-025-01289-5","url":null,"abstract":"<p><strong>Background: </strong>Sarcomas represent a heterogeneous group of mesenchymal tumors that, despite accounting for only 1% of cancers worldwide, rank among the top five causes of cancer-related deaths in patients under 20 years old. Surgical resection remains the primary treatment for these malignancies, as effective systemic therapies are limited, particularly for high-grade disease. However, surgical outcomes are often compromised by incomplete resection, leading to high local and distal recurrence rates. Intraoperative molecular imaging has emerged as a promising approach to improve surgical outcomes but has been hindered by the lack of tumor-specific targeting agents. Fibroblast activation protein (FAP), selectively expressed by mesenchymal tumors and absent in healthy tissues, presents a promising target for fluorescence-guided cancer resections.</p><p><strong>Results: </strong>We demonstrate that 41% of human sarcomas express FAP, with expression correlating with higher histologic grade. The FAP-S0456 optical tracer specifically bound to FAP-expressing sarcomas with minimal binding to normal tissues, exhibiting excellent tumor-to-background ratios (3.8 ± 0.43). In vitro studies confirmed FAP-S0456's specificity for human FAP with a dissociation constant of approximately 10 nM. In murine xenograft models, the tracer accurately identified both primary tumors and pulmonary metastases of FAP-expressing sarcomas. Importantly, using needle confocal laser endomicroscopy, we demonstrated that FAP-S0456 enables real-time, single-cell visualization of metastatic tumor cells during surgery, including micrometastases not detected by conventional imaging.</p><p><strong>Conclusions: </strong>FAP-S0456 represents a promising molecular imaging agent for the detection and surgical removal of primary and metastatic sarcomas. Its high specificity for FAP-expressing tumor cells, favorable biodistribution profile, and ability to detect microscopic disease offer potential to improve complete surgical resection. These findings support the development of FAP-targeted fluorescence-guided surgery for sarcoma patients, which may lead to improved oncologic outcomes, particularly for those with pulmonary metastases where complete surgical clearance is critical for survival.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"94"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728788","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}
EJNMMI ResearchPub Date : 2025-07-26DOI: 10.1186/s13550-025-01287-7
Felicitas J Bijari, Paul Kyu Han, Thibault Marin, Wonil Lee, Yanis Chemli, Inna Gertsenshteyn, Ismaël B G Mounime, Yanis Djebra, Didi Chi, Marc D Normandin, Chao Ma, Georges El Fakhri
{"title":"In vivo 3D myocardial membrane potential mapping in humans using PET/MRI.","authors":"Felicitas J Bijari, Paul Kyu Han, Thibault Marin, Wonil Lee, Yanis Chemli, Inna Gertsenshteyn, Ismaël B G Mounime, Yanis Djebra, Didi Chi, Marc D Normandin, Chao Ma, Georges El Fakhri","doi":"10.1186/s13550-025-01287-7","DOIUrl":"10.1186/s13550-025-01287-7","url":null,"abstract":"<p><strong>Background: </strong>The mitochondrial membrane potential is a key biophysical parameter of mitochondrial function, which can be useful for the diagnosis and treatment monitoring of various cardiac diseases. We present a non-invasive PET/MR imaging method for 3D myocardial membrane potential mapping in humans.</p><p><strong>Results: </strong>An in vivo PET/MR imaging study was performed in three healthy subjects (1 male and 2 females; 48 ± 29 years old) under a study protocol approved by the local Institutional Review Board (IRB). Written informed consent was obtained from all subjects before participation in the study. The [<sup>18</sup>F](4-Fluorophenyl)triphenylphosphonium ([<sup>18</sup>F]-FTPP<sup>+</sup>) PET tracer was administered using a bolus-plus-infusion protocol (bolus activity of 301.2 ± 7.6 MBq, infusion activity of 90.0 ± 4.9 MBq), where an infusion of 120 min was started shortly after the bolus injection (time of infusion, TOI). Dynamic cardiac PET/MR imaging was performed approximately 20 min after the TOI and continued for 100 min. The extracellular volume fraction mapping was performed via cardiac MR with a free-breathing, 3D cardiac T<sub>1</sub> mapping sequence before and after the contrast agent injection (gadoterate meglumine, 0.1 mmol/kg). A linear tangent space alignment (LTSA) model-based method was used to reconstruct high-frame-rate dynamic images from sparsely sampled (k,t)-space data for T<sub>1</sub>. PET motion correction was performed using two steps of rigid image registration in a multi-resolution fashion, followed by a non-rigid image registration with B-spline transform. The tissue membrane potential was calculated using a kinetic model based on the Nernst equation with myocardial tracer concentration, tracer volume of distribution, and extracellular volume fraction measurements. Fully 3D membrane potential maps were successfully estimated from all three subjects. The estimated whole-heart membrane potentials were - 144.7 ± 3.5 mV, - 160.7 ± 5.3 mV, and - 165.8 ± 3.1 mV for each subject.</p><p><strong>Conclusion: </strong>The proposed method allows 3D myocardial membrane potential mapping in humans in vivo.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"93"},"PeriodicalIF":3.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717744","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}
EJNMMI ResearchPub Date : 2025-07-24DOI: 10.1186/s13550-025-01265-z
Matthew J Roberts, Natasha A Roberts, Anita Pelecanos, John W Yaxley, Simon J D Harley, Amila R Siriwardana, Karla Cullen, Marita Prior, Karen Lindsay, Ian Vela, Anna Kuchel, Nattakorn Dhiantravan, Paul Thomas, David A Pattison
{"title":"A prospective, multi-centre trial of PSMA-PET compared to FDG-PET for staging of newly diagnosed high risk prostate cancer.","authors":"Matthew J Roberts, Natasha A Roberts, Anita Pelecanos, John W Yaxley, Simon J D Harley, Amila R Siriwardana, Karla Cullen, Marita Prior, Karen Lindsay, Ian Vela, Anna Kuchel, Nattakorn Dhiantravan, Paul Thomas, David A Pattison","doi":"10.1186/s13550-025-01265-z","DOIUrl":"10.1186/s13550-025-01265-z","url":null,"abstract":"<p><strong>Background: </strong>Despite being a potentially attractive alternative molecular imaging modality due to wider availability and association with lethal disease in advanced prostate cancer, the role of fluorodeoxyglucose (FDG)- positron emission tomography (PET) at initial diagnosis compared to Prostate Specific Membrane Antigen (PSMA) PET is yet to be accurately determined. The aim of this study was to evaluate the additive benefit of FDG PET to PSMA PET in patients with newly diagnosed, high risk prostate cancer.</p><p><strong>Results: </strong>A prospective trial conducted across three sites between October-2021 and January-2023 recruited 32 participants with high risk (EAU classification) prostate cancer staged with PSMA PET-CT. FDG PET-CT was acquired centrally and reported with a standardised template. Median age was 69 years, median PSA was 14 ug/L, and most had PI-RADS 5 scores (59%) and ISUP Grade Group 5 tumours (66%). Overall, FDG-PET did not detect any additional definite/probable metastasis according to physician interpretation. All tumours showed PSMA avidity and higher stage was observed per PSMA-PET in 5 participants. No FDG uptake at the primary tumour occurred in 34% of participants. FDG-PET did not result in a change in management for any participant. PSA remission rates were lower in patients with stage ≥ 3 tumours on MRI (60% vs 94%, p = 0.04). Patient reported outcomes (PROs) were largely stable throughout the study.</p><p><strong>Conclusions: </strong>FDG-PET did not provide additive staging information above PSMA-PET or alter management for newly diagnosed high-risk prostate cancer patients.</p><p><strong>Trial registration number: </strong>ANZCTR ACTRN12621001185853. Registered 03-09-2021. Available at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382299.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"92"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697912","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}
EJNMMI ResearchPub Date : 2025-07-23DOI: 10.1186/s13550-025-01288-6
Stefan E Poirier, Rachel Wagner, Linshan Liu, Pavlo Ohorodnyk, Michael T Jurkiewicz, Alexander Thiel, Jonathan D Thiessen, Alexander V Khaw, Udunna C Anazodo
{"title":"Association of white matter injury and neuroinflammation in the post-acute phase after ischemic stroke using [<sup>18</sup>F]FEPPA-PET/MRI.","authors":"Stefan E Poirier, Rachel Wagner, Linshan Liu, Pavlo Ohorodnyk, Michael T Jurkiewicz, Alexander Thiel, Jonathan D Thiessen, Alexander V Khaw, Udunna C Anazodo","doi":"10.1186/s13550-025-01288-6","DOIUrl":"10.1186/s13550-025-01288-6","url":null,"abstract":"<p><strong>Background: </strong>Cerebral white matter (WM) injury after ischemic stroke is associated with post-stroke cognitive impairment (PSCI), however, the interaction between sustained neuroinflammation and post-stroke WM injury is not well understood. Hybrid PET/MRI can provide insight into pathophysiological mechanisms linking chronic neuroinflammation, ischemic WM injury, and PSCI. Using PET/MRI, this study investigated the relationship between [<sup>18</sup>F]FEPPA standardized uptake value ratio (SUVr) measurements of glial activation and diffusion tensor imaging (DTI) measurements of microstructure integrity in brain WM regions in the chronic phase at 6-months after acute ischemic stroke.</p><p><strong>Results: </strong>[<sup>18</sup>F]FEPPA-PET, DTI, and T2-weighted FLAIR were acquired at 6-months post-stroke in 19 elderly humans (seven females; mean age = 76 ± 5 years) with confirmed first-ever acute ischemic stroke using hybrid PET/3T-MRI. Index infarcts, chronic (incidental, covert) infarcts, and WM hyperintensities were manually segmented on FLAIR and excluded from the imaging analysis. Pearson correlation was conducted to assess the association between [<sup>18</sup>F]FEPPA-SUVr and DTI measurements in WM regions commonly implicated in PSCI. [<sup>18</sup>F]FEPPA-SUVr was elevated in brain regions ipsilateral to the index infarct at 6-months post-stroke, and these increases correlated with decreases in fractional anisotropy in several WM pathways linked to PSCI, including right superior longitudinal fasciculus (SLF) III (r = -0.82, p < 0.0001), right anterior thalamic radiation (r = -0.61, p = 0.006), and right arcuate fasciculus (r = -0.56, p = 0.01). Elevated [<sup>18</sup>F]FEPPA-SUVr was also associated with increased mean diffusivity (r = 0.69, p < 0.001), axial diffusivity (r = 0.55, p = 0.02), and radial diffusivity (r = 0.74, p < 0.001) in right SLF III.</p><p><strong>Conclusions: </strong>This study found an association between elevated post-acute glial activation (neuroinflammation) and reduced microstructure integrity in brain WM pathways ipsilateral to ischemic infarcts and remote from WM lesions at 6-months post-stroke. Hybrid PET/MRI is promising to be a valuable tool for probing post-acute neuroinflammation and associated changes in cerebral WM pathways following ischemic stroke.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"91"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689587","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}
EJNMMI ResearchPub Date : 2025-07-22DOI: 10.1186/s13550-025-01279-7
Korbinian Krieger, Thomas Pyka, Clemens Mingels, Hasan Sari, Albert Gjedde, Axel Rominger, Paul Cumming
{"title":"Kinetics of the amino acid uptake tracer O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine (FET) in human brain.","authors":"Korbinian Krieger, Thomas Pyka, Clemens Mingels, Hasan Sari, Albert Gjedde, Axel Rominger, Paul Cumming","doi":"10.1186/s13550-025-01279-7","DOIUrl":"10.1186/s13550-025-01279-7","url":null,"abstract":"<p><strong>Background: </strong>The large neutral amino acid [<sup>18</sup>F]fluoroethoxy-L-tyrosine ([<sup>18</sup>F]FET) is a popular tracer for detection and staging of intracranial tumors by positron emission tomography (PET). While its high tumoral uptake reflects over-expression of the L-type amino acid transporter (LAT1), there is little knowledge about the kinetics of [<sup>18</sup>F]FET uptake in healthy brain tissue, owing to the limited PET data in healthy volunteers, and to the requirement of an arterial input function for compartmental analysis. To address this, we used long axial field-of-view (LAFOV) dynamic 40-min recordings of 28 post-operative patients with intracranial tumors to undertake parametric brain mapping relative to an image-derived arterial input function (IDIF) obtained from the aorta. We averaged the individual parametric maps to obtain estimates of the physiological uptake relatively unaffected by individual residual lesions and resections, and tested simplified single-frame methods for quantitation.</p><p><strong>Results: </strong>The analyses yielded estimates of regional unidirectional blood-brain clearance K<sub>1</sub> (0.00825-0.0244 ml g<sup>-1</sup> min<sup>-1</sup>), net blood-brain clearance K<sub>in</sub> (0.00448-0.00913 ml g<sup>-1</sup> min<sup>-1</sup>), and equilibrium distribution volume V<sub>T</sub> (0.126-0.495 ml g<sup>-1</sup>), where the lowest values depict white matter, and the highest values cerebellum. In our test of a simplified quantitation of [<sup>18</sup>F]FET uptake from single frame recordings, i.e., Gjedde-Patlak multilinear graphic analyses of K<sub>1</sub> at five min post-injection and K<sub>in</sub> at 40 min post injection, results were in good agreement with the analyses from the dynamic recordings (< 10% error).</p><p><strong>Conclusions: </strong>Compartmental analysis results for [<sup>18</sup>F]FET uptake in extra-tumoral human brain regions are in accord with the few prior reports, mainly obtained in experimental animals, and support the use of single frame quantitation. Present findings in relatively healthy brain should inform the interpretation of pathological [<sup>18</sup>F]FET uptake in tumors.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"90"},"PeriodicalIF":3.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689588","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 myocardial fibrosis and wall motion abnormality with <sup>68</sup>Ga-FAPI PET/MR in coronary heart disease.","authors":"Rui Luo, Zhenyu Zhao, Chuan Zhang, Ru-Shuai Li, Yanrong Wang, Qingle Meng, Yudan Ni, Bolin Wang, Lanhua Li, Luan Feng, Rui Yang, Lin Xie, Xin Chen, Ming-Rong Zhang, Feng Wang","doi":"10.1186/s13550-025-01246-2","DOIUrl":"10.1186/s13550-025-01246-2","url":null,"abstract":"<p><strong>Background: </strong>To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/MR in coronary heart disease (CHD) and its association with abnormal wall motion.</p><p><strong>Results: </strong>In this prospective study, participants with CHD after PCI (Percutaneous Coronary Intervention) underwent gallium 68 (<sup>68</sup> Ga)-labeled FAPI PET/MR imaging. FAP signal was quantified using standardized uptake values. Cardiac MRI yielded functional parameters and area of injury (MRI non-viable). Abnormal wall motion identified by myocardial strain analysis was evaluated using integrated analysis of late gadolinium enhancement (LGE) and FAP signal. The correlations between FAP signal and clinical parameters were explored. Forty-two participants were included and FAP signal was higher in left ventricle regional myocardium compared with remote normal areas (SUVmax, 5.0 ± 1.8 vs 1.2 ± 0.4; p < .001). In total, 432 segments (432/714, 60.50%) displayed impaired wall motion. In integrated analysis, the highest wall motion abnormality score was observed in the FAPI active/MRI non-viable group (11.0 ± 5.2). FAP signal was positively correlated with K time (SUVpeak: R = 0.48; p = .046; SUVmean: R = 0.57; p = .014) and negatively correlated with Angle (SUVpeak: R = - 0.52; p = .026; SUVmean: R = - 0.56; p = .026) in thromboelastography. Immunohistochemical analysis revealed FAP-positive fibroblasts in the infarct and border zone, and robust expression of α-smooth muscle actin and vimentin.</p><p><strong>Conclusions: </strong>Simultaneous <sup>68</sup> Ga- FAPI PET/MR offers novel insights into the regional pattern of fibroblast activation in CHD, and the fibroblast activation protein signal is associated with abnormal wall motion. Trial registration ClinicalTrials: ClinicalTrials.gov ID: NCT05867589. Registered 01 May 2023, https://clinicaltrials.gov/study/NCT05867589.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"89"},"PeriodicalIF":3.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674179","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}