EJNMMI Research最新文献

{"title":"Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction.","authors":"Putri Andriana, Senthil Palani, Heidi Liljenbäck, Imran Iqbal, Vesa Oikonen, Jenni Virta, Konstantina Makrypidi, Johan Rajander, Erika Atencio Herre, Aino Suni, Sirpa Jalkanen, Juhani Knuuti, Luisa Martinez-Pomares, Ioannis Pirmettis, Xiang-Guo Li, Antti Saraste, Anne Roivainen","doi":"10.1186/s13550-025-01254-2","DOIUrl":"10.1186/s13550-025-01254-2","url":null,"abstract":"<p><strong>Background: </strong>The macrophage mannose receptor (CD206) is expressed predominantly on the surface of M2-type macrophages, which play a role in resolution of inflammation after myocardial injury. The purpose of this study was to evaluate the utility of CD206-targeted PET tracer Al[¹⁸F]F-NOTA-D10CM, a fluorinated mannosylated dextran derivative, for imaging immune responses after experimental acute myocardial infarction (MI).</p><p><strong>Results: </strong>Flow cytometry revealed selective binding of Alexa-488-NOTA-D10CM to human M2-polarized macrophages derived from blood monocytes compared to M1 macrophages. The binding affinity of Al[¹⁸F]F-NOTA-DCM for CD206-positive Chinese hamster ovary cells was 1.83 ± 0.68 nM. In vivo PET and ex vivo autoradiography experiments in Sprague-Dawley rats studied at 3 and 7 days after permanent ligation of the left coronary artery or a sham-operation, showed significantly higher uptake of Al[¹⁸F]F-NOTA-DCM in the MI area than in remote areas, or the myocardium of sham-operated rats. However, there was no difference in uptake in the MI area between day 3 and day 7. Uptake of Al[¹⁸F]F-NOTA-DCM in the MI area correlated positively with the area-% of CD206-positive staining of the left ventricular myocardium (r = 0.481, P = 0.006). In vitro competition studies on tissue cryosections using a molar excess of unlabeled D10CM revealed a reduction of approximately 85%, confirming specific tracer binding.</p><p><strong>Conclusion: </strong>Al[¹⁸F]F-NOTA-D10CM PET detects overexpression of CD206 after ischemic myocardial injury, and may be a suitable biomarker for detecting M2-type macrophages associated with the inflammatory process post-MI.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"66"},"PeriodicalIF":3.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215293","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":"Augmentation of [¹⁸F]-C-SNAT4 PET imaging of apoptosis after radiotherapy using a cold mixing strategy.","authors":"Jeffrey Qiu, Min Chen, Zixin Chen, Corinne Beinat, Stavros Melemenidis, Edward Graves, Jianghong Rao","doi":"10.1186/s13550-025-01255-1","DOIUrl":"10.1186/s13550-025-01255-1","url":null,"abstract":"<p><strong>Background: </strong>Positron Emission Tomography (PET) imaging can monitor cancer treatment response by non-invasively detecting apoptosis in vivo. Signal-to-noise (SNR) remains one of the critical barriers to approval for clinical use. We have previously developed a PET tracer [18 F]-C-SNAT4 for imaging capase-3 activity in apoptotic tumors induced by chemo- and immunotherapy. [18 F]-C-SNAT4 is designed to undergo caspase-3 activated intramolecular cyclization. The product then self-assembles in situ into nanoparticles to generate preferential retention of F18 radioactivity in apoptotic cells. This unique mechanism prompted us to investigate if a cold mixture could enhance the probe retention and further augment the sensitivity for imaging radiotherapy.</p><p><strong>Results: </strong>[18 F]-C-SNAT4 and hot/cold mixture [18 F]/[19 F]-C-SNAT4 were used to detect human NSCLC (NCI-H460) apoptosis induced by radiation. Both hot [18 F]-C-SNAT4 and hot/cold mixture [18 F]/[19 F]-C-SNAT4 had significantly increased uptake in radiation treated vs. untreated NCI-H460 cells in vitro. A 1: 80 hot/cold mixture increased signal by 1.6x compared to [18 F]-C-SNAT4 alone. In vivo studies were performed in murine xenograft models in high-dose radiation and low-dose radiation treatment groups. The hot/cold mixture showed an increase in the signal by 2.5x in high-dose radiation treated murine NCI-H460 xenograft models. Low-dose radiation induced apoptosis was only detected with the hot/cold mixture with 2.4x signal compared to hot [18 F]-C-SNAT4. Toxicity and dosimetry safety were evaluated at 250x and 10x respective dosages, then normalized to human dose equivalent.</p><p><strong>Conclusion: </strong>A hot/cold mixture of [18 F]/[19 F]-C-SNAT4 generates significantly more signal compared to hot [18 F]-C-SNAT4, leading to higher sensitivity in detecting treatment response. This may present a solution to low sensitivity in the translation of apoptosis-specific radionuclides to clinical application.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"65"},"PeriodicalIF":3.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207927","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 effect of three-dimensional left ventricular mechanical dyssynchrony and cardiac sympathetic denervation in systolic heart failure risk-stratified by left ventricular ejection fraction and QRS duration.","authors":"Takahiro Doi, Koki Morishita, Rintaro Furuoka, Kosuke Uruno, Ryosuke Hatano, Mirei Nabuchi, Ken Masuda, Kaoru Komuro, Hiroyuki Iwano, Daigo Nagahara, Satoshi Yuda, Akiyoshi Hashimoto, Tomoaki Nakata","doi":"10.1186/s13550-025-01257-z","DOIUrl":"10.1186/s13550-025-01257-z","url":null,"abstract":"<p><strong>Background: </strong>The left ventricular ejection fraction (LVEF) and QRS duration (QRSd) are prognostic factors in patients with systolic heart failure (HF). However, no study has evaluated the prognosis was evaluated by adding three-dimensional left ventricular mechanical dyssynchrony (LVMD) and cardiac sympathetic dysfunction.</p><p><strong>Results: </strong>In 1011 consecutive patients with HF having LVEF < 50%, LVMD was evaluated as the phase SD of the regional onset-of-mechanical contraction phase angles on a phase histogram created by Fourier phase analysis applied to regional time-activity curves obtained by gated myocardial perfusion. ¹²³I- meta-iodobenzylguanidine scintigraphy was also performed in all cases. Patients were followed up with a primary endpoint of lethal cardiac events (CEs). During the follow-up period (44 months), CEs were documented in 315 of the patients with HF. The CE group had a greater phase SD and lower standardized late heart-to-mediastinal ratio (slHMR) than the non-CE group. Phase SD and slHMR were identified by overall multivariate analysis to be significant prognostic determinants. ROC curve analyses revealed cutoff values of 36° for phase SD and 1.89 for slHMR for identifying patients with high-risk HF. Patients with HF and both phase SD > 36° and slHMR < 1.89 showed a significantly higher CE rate than other patients in the overall population, and patients' CE rates were divided into four groups according to the cutoff values of LVEF (35%) and QRSd (130 ms).</p><p><strong>Conclusions: </strong>The addition of three-dimensional LVMD and cardiac sympathetic function to the evaluation of LVEF and QRSd in patients with systolic HF may stratify the risk of their prognosis.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"64"},"PeriodicalIF":3.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207928","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":"PARP1-targeted alpha therapy enhances target expression.","authors":"Hasan Babazada, Paul Martorano, Hsiaoju Lee, Shuyao Geng, Vandana Batra, John M Maris, Daniel A Pryma, Sarah B Gitto, Michael D Farwell","doi":"10.1186/s13550-025-01256-0","DOIUrl":"10.1186/s13550-025-01256-0","url":null,"abstract":"","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"63"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198557","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":"Kinetic modeling of ¹⁸F-PI-2620 binding in the brain using an image-derived input function with total-body PET.","authors":"Anjan Bhattarai, Emily Nicole Holy, Yiran Wang, Benjamin A Spencer, Guobao Wang, Charles DeCarli, Audrey P Fan","doi":"10.1186/s13550-025-01260-4","DOIUrl":"10.1186/s13550-025-01260-4","url":null,"abstract":"<p><strong>Background: </strong>Accurate quantification of tau binding from ¹⁸F-PI-2620 PET requires kinetic modeling and an input function. We aimed to implement a non-invasive Image-derived input function (IDIF) using the state-of-the-art total-body uEXPLORER PET/CT scanner to quantify tau binding and tracer delivery rate from ¹⁸F-PI-2620 in the brain. Additionally, we investigated the impact of scan duration on the quantification of kinetic parameters.</p><p><strong>Results: </strong>¹⁸F-PI-2620 total-body PET dynamic (90 min) data from 15 elderly (66-92 years) participants were acquired. Time-activity curves were obtained from grey matter regions of interest (ROIs) known to be affected in Alzheimer's disease, including the medial temporal lobe, posterior cingulate, and lateral parietal cortex. These curves were fitted to the two-tissue compartmental model (2TCM) using a subject-specific IDIF (plasma and metabolite corrected) derived from the descending aorta. ROI-specific kinetic parameters were estimated for different scan durations ranging from 10 to 90 min. The parameters included blood fraction volume (v_b), rate constants (K₁, k₂, k₃, k₄), total distribution volume (V_T), distribution volume ratio (DVR), and tracer arrival delay. Logan graphical analysis was also used to estimate V_T and compared with 2TCM. Differences in kinetic parameters were observed between ROIs, including significant reduction in tracer delivery rate (K₁) in the medial temporal lobe (q < 0.001). All kinetic parameters remained relatively stable (compared to parameters quantified with full 90-minute data) after the 60-minute scan window across all ROIs (r ≥ 0.89; p < 0.001), with K₁ showing high stability after 30 min of scan duration (r ≥ 0.92; p < 0.001). Excellent correlation was observed between V_T estimated using 2TCM and Logan plot analysis (r ≥ 0.96; p < 0.001).</p><p><strong>Conclusions: </strong>This study demonstrated the utility of IDIF from a lager blood pool, derived using the total-body PET in quantifying ¹⁸F-PI-2620 kinetics in the brain. Our findings suggest that a 60-minute scan window may be required for the reliable quantification of kinetic parameters using IDIF, whereas a 30-minute scan time may be sufficient for the quantification of K₁.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"62"},"PeriodicalIF":3.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186808","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":"Biphasic contrast-enhanced [¹⁸F]PSMA-1007 PET/CT imaging to improve the detection of local relapse of prostate cancer.","authors":"Eduards Mamlins, Emil Novruzov, Tadashi Watabe, Yuriko Mori, Mardjan Dabir, Katalin Mattes-György, Christina Antke, Jan Henke, Matthias Boschheidgen, Julian Kirchner, Danny Jazmati, Jan Hausmann, Jan P Radtke, Günter Niegisch, Jens Cardinale, Juliane Hörner-Rieber, Peter Albers, Gerald Antoch, Frederik L Giesel, Lars Schimmöller","doi":"10.1186/s13550-025-01252-4","DOIUrl":"10.1186/s13550-025-01252-4","url":null,"abstract":"<p><strong>Background: </strong>The implementation of PSMA imaging in prostate cancer (PC) management has significantly improved the medical care of patients owing to its clinical impact, particularly with respect to biochemical recurrence. However, there is still an unmet clinical need regarding the correct discrimination of equivocal, centrally located, focal [¹⁸F]PSMA-1007 uptake without any CT-morphological findings in the postsurgical prostate bed. The aim of this monocentric, retrospective study was to investigate the efficacy of a biphasic, contrast-enhanced [¹⁸F]PSMA-1007 acquisition protocol.</p><p><strong>Results: </strong>This study investigated a total of 24 biologically male patients with BCR, with a mean PSA level of 0.96 ng/ml at the time of recurrence. The presence of local relapse was regarded as consistent by biphasic, contrast-enhanced [¹⁸F]PSMA-1007 PET/CT scans, of which 22 cases were finally validated through the composite reference standard after a 2-years follow-up. The acquisition of whole-body, contrast-enhanced PET/CT imaging data was performed after a mean of 105 (± 19) minutes, whereas late-phase PET/CT imaging of the pelvis with low-dose CT was conducted after 140 min (± 10) on average following the intravenous application of [¹⁸F]PSMA-1007 (injected mean activity of 240 MBq (± 29)). The median SUV_max and SUV_mean values of local relapse increased by 26% and 5%, respectively, in late-phase images. Moreover, median TBR with respect to the obturator internus muscle seemed to benefit the most from late-phase imaging, with an increase of 185%. The dynamics of the SUV metrics and TBR in lesions were statistically significant (P value < 0.001-0.019). Moreover, the retrospective reading of delayed [¹⁸F]PSMA-1007 PET/CT imaging provided an upgrade of the reporting for suspected local PC relapse from a previous PSMA-RADS 3A to a later PSMA-RADS 5 in seven patients (29%), unless the impact of contrast agent in the urethra would also be considered equally important. For the remaining patients, the qualitative evaluation of contrast agent displacement in the urethra was necessary for a final clinical decision that provided the upgrading of the reporting to PSMA RADS 5 for an additional nine patients (38%).</p><p><strong>Conclusions: </strong>Given the aforementioned, highly specific unmet clinical need for a relatively small ratio of patients with prostate cancer undergoing PSMA imaging, our proposed acquisition protocol mandates a well-balanced preselection of patients. Under this premise, the study results demonstrated that the optimized acquisition protocol with biphasic contrast-enhanced [¹⁸F]PSMA-1007 PET/CT imaging improved the diagnostic performance for the detection of local PC recurrence in 67% of preselected patients.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"61"},"PeriodicalIF":3.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186807","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":"Metabolic parameters on baseline and early [¹⁸F]FDG PET/CT as a predictive biomarker for resistance to BRAF/MEK inhibition in advanced cutaneous BRAFV600-mutated melanoma.","authors":"Bernies van der Hiel, Berlinda J de Wit-van der Veen, Alfons J M van den Eertwegh, Wouter V Vogel, Marcel P M Stokkel, Marta Lopez-Yurda, Ronald Boellaard, Ellen W Kapiteijn, Geke A P Hospers, Maureen J B Aarts, Filip Y F L de Vos, Marye J Boers-Sonderen, Astrid A M van der Veldt, Jan Willem B de Groot, John B A G Haanen","doi":"10.1186/s13550-025-01259-x","DOIUrl":"10.1186/s13550-025-01259-x","url":null,"abstract":"<p><strong>Background: </strong>[¹⁸F]FDG PET/CT plays a crucial role in evaluating cancer patients and assessing treatment response, including in BRAF-mutated melanoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have emerged as promising alternatives to standardized uptake value (SUV)-based measures for tumor assessment. This study evaluates the predictive value of SUVpeak, MTV, and TLG in predicting progression-free survival (PFS) in advanced BRAF-mutated melanoma treated with BRAF/MEK inhibitors.</p><p><strong>Results: </strong>Seventy-five patients with metastatic melanoma were enrolled in a multi-center trial and treated with vemurafenib/cobimetinib. [¹⁸F]FDG-PET/CT scans were performed at baseline, week-2, and week-7. Imaging analysis included SUVpeak, MTV, and TLG of summed metastases, as well as percentage changes over time (∆). Baseline median PET-parameters were SUVpeak 12.59 (range 3.13-50.59), MTV 159mL (range 0-1897 mL), and TLG 1013 (range 1-13162). Baseline MTV was the strongest predictor (AUC_{T=6 months}=0.714), while early changes in MTV, TLG, and especially week-7 ΔSUVpeak% showed similar or improved performance (P = 0.017 vs. baseline SUVpeak). Patients with TLG below the median had significantly prolonged PFS (15.4 vs. 8.5 months, P = 0.024). MTV above optimal cutoff (45.3 mL) was associated with an increased risk of progression/death, even after adjusting for LDH, ECOG status, and metastatic sites (HR = 2.97, 95% CI 1.17-7.52, P = 0.022). At week-2, ∆SUVpeak% was not predictive in a multivariable analysis, but became predictive at week-7 (median ∆SUVpeak%: 64), with a more than three-fold hazard of progression for patients with ∆SUVpeak% below 64% (P = 0.0014); PFS was 5.0 months (95% CI: 4.3-NA) for patients below the median versus 14.7 months (95% CI: 9.2-20.2) for those above or with non-quantifiable scans (P = 0.0002). Median ∆MTV was 95.5% at week-2 and 97.6% at week-7, with significant PFS differences at both time points (week-2: P = 0.020, week-7: P < 0.001). As expected, TLG mirrored MTV. Patients with MTV increases at week-7 after an initial response at week-2 had a median PFS of 5.3 vs. 12.6 months for those with stable or declining MTV (P = 0.0023). Intra-patient metabolic heterogeneity was also associated with outcome, with early reductions in SUVpeak variation between lesions correlating with better PFS.</p><p><strong>Conclusion: </strong>This study supports the use of MTV and TLG as robust predictive markers for PFS in advanced melanoma treated with BRAF/MEK-inhibitors. Monitoring early PET parameters changes can provide valuable insights into therapeutic response and disease progression.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"60"},"PeriodicalIF":3.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157370","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 protection considerations with [⁸⁹Zr]Zr-girentuximab PET and surgery.","authors":"Adnan Chowdhury, Clément Morgat, Clement Bailly, John Sunderland, Stephen A Graves, Andrew M Scott, Sean Baker, Beverley F Holman","doi":"10.1186/s13550-025-01247-1","DOIUrl":"10.1186/s13550-025-01247-1","url":null,"abstract":"<p><strong>Background: </strong>⁸⁹Zr is emerging as a popular positron-emitting radionuclide for imaging; however, its 909 keV gamma emission presents shielding challenges, and radiation exposure safety guidelines for healthcare professionals working with the radionuclide have not been well-established. To guide assessment of the radiation risk and necessary safety guidelines, we present laboratory dose rate measurements of ⁸⁹Zr syringes and vials, and dose rates measurements made during the ZIRCON clinical trial ([⁸⁹Zr]Zr-girentuximab) to evaluate healthcare provider exposure during administration, imaging, and surgical procedures.</p><p><strong>Results: </strong>The maximum dose rate from a vial with no shielding was 0.334 µSv/h/MBq, and the minimum dose rate with 66 mm lead shielding was 0.004 µSv/h/MBq. The controlled spill measured 0.52 µSv/h/MBq. Dose rates 1 m from patients who received [⁸⁹Zr]Zr-girentuximab had an average of 3.90 µSv/h at imaging. During surgery, waste measured below background levels, and a bed assistant 0.8 m from the patient received a 5 µSv/h whole-body dose rate. The excised kidney measured 6 µSv/h at 5 cm.</p><p><strong>Conclusions: </strong>Our results demonstrate low radiation exposure levels associated with ⁸⁹Zr handling and exposure to the patient. With potential integration of ⁸⁹Zr into clinical practice, appropriate radiation safety guidelines are needed. Dose rate measurements can help guide development of best practices and site-specific protocols.</p><p><strong>Clinical trial number: </strong>not applicable for this study; ZIRCON trial number NCT03849118, registered on 19 February 2019.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"15 1","pages":"59"},"PeriodicalIF":3.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127023","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":"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}