EJNMMI Research最新文献

Background: The aim is to develop and validate radiomics based on 2-[¹⁸F]fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) parameters for predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC).

Methods: A total of 209 patients with 214 lesions, who underwent 2-[¹⁸F]FDG PET/CT scans between December 2016 to December 2023, were included in our study. All ccRCC lesions were categorized into low grade (WHO/ISUP grade I-II) and high grade (WHO/ISUP grade III-IV). The lesions were allocated into a training group and a testing group in a ratio of 7:3. The radiomics features were extracted by a serious of maximum standardized uptake value (SUVmax) thresholds (0,2.5%,25%,40%) with the utilization of the minimum redundancy and maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithm. The clinical, radiomics and combined models were constructed. The receiver operating characteristic (ROC) curve, decision curve and calibration curves were plotted to assess the predicting performance.

Results: The area under curve (AUC) of PET-0, PET-2.5%, PET-25%, PET-40% model in the training group were 0.881(95% CI: 0.822-0.940),0.883(95% CI: 0.825-0.942),0.889(95% CI: 0.831-0.946),0.887(95% CI: 0.826-0.948); and 0.878(95% CI: 0.777-0.978),0.876(95% CI: 0.776-0.977),0.871(95% CI: 0.769-0.972),0.882(95% CI: 0.786-0.979) in the testing group. Due to perfect prediction and verification performance, the volume of interest (VOI) from PET images with SUVmax threshold of 40% were selected to construct the radiomics model and combined model. The AUC of the clinical model and radiomics model was 0.859 (sensitivity = 0.846, specificity = 0.747) and 0.909 (sensitivity = 0.808, specificity = 0.751) in the training group, respectively; 0.882 (sensitivity = 0.857, specificity = 0.857) and 0.901 (sensitivity = 0.905, specificity = 0.833) in the testing group, respectively. In combined models, the AUC was 0.916, the sensitivity was 0.923 and the specificity was 0.808 in the training group; the AUC was 0.916, the sensitivity was 0.881 and the specificity was 0.792 in the training group.

Conclusion: Radiomics based on 2-[¹⁸F]FDG PET/CT can be helpful to predict WHO/ISUP grade of ccRCC.

Background: Symptoms in acute cerebral sinus venous thrombosis (CSVT) are highly variable, ranging from headaches to fatal stroke, and the basis for this high inter-individual variability is poorly understood. The present study aimed to assess whether acute CSVT significantly alters regional cerebral blood flow (CBF), if findings differ from CBF patterns know from large-artery occlusion in stroke, and whether the pattern of CBF alterations depends on clot location. Therefore, we retrospectively analyzed 12 patients with acute CSVT 10.6 ± 4.6 days after symptom onset and ten healthy volunteers who underwent [¹⁵O]water PET (two scans each, 300 ± 14 MBq [¹⁵O]water). Static image datasets (15-75 s after injection; normalized to cerebellum) reflecting relative CBF (rCBF) were analyzed using voxel- and region-of-interest-based analysis (AAL3-atlas). We mirrored datasets of patients with left-sided CSVT to harmonize the affected hemisphere.

Results: Seven and five patients showed right- and left-sided CSVT, respectively. The superior sagittal sinus (SSS) was involved in 8/12 patients. CSVT patients had extensive rCBF deficits in the voxel-based analysis with accentuation in the right (ipsilateral) frontal cortex and caudate nucleus compared to controls, which were most pronounced in cortical areas in those with involvement of the SSS (8/12), and in subcortical areas in those without involvement of the SSS (4/12; p < 0.05, false discovery rate corrected). ROI-analysis demonstrated significant frontal (p = 0.01) and caudate nucleus (p = 0.008) rCBF deficits driven by patients with and without SSS occlusion, respectively.

Conclusions: [¹⁵O]water PET was able to visualize characteristic patterns of impaired rCBF, which were different from intracranial large-artery occlusion in acute ischemic stroke, and exhibited substantial rCBF alterations depending on the involvement of the SSS. Our findings provide novel insights into the effects of disturbed venous drainage on CBF in acute CSVT, which may aid in understanding the pathophysiology, and guide future therapy of acute CSVT.

Background: This multicentre retrospective observational study aims to develop imaging-based prognostic and predictive models for relapsed/refractory (R/R) B-cell lymphoma patients undergoing CAR-T therapy by integrating clinical data and imaging features. Specifically, our aim was to predict 3- and 6-month treatment response, overall survival (OS), progression-free survival (PFS), and the occurrence of the immune effector cell-associated neurotoxicity syndrome (ICANS).

Results: Sixty-five patients of R/R B-cell lymphoma treated with CAR-T cells in two centres were included. Pre-infusion [¹⁸F]FDG PET/CT scans and clinical data were systematically collected, and imaging features, including kurtosis, entropy, maximum diameter, standardized uptake value (SUV) related features (SUV_max, SUV_mean, SUV_std, SUV_median, SUV_p25, SUV_p75), total metabolic tumour volume (MTV_total), and total lesion glycolysis (TLG_total), were extracted using the Quibim platform. The median age was 62 (range 21-76) years and the median follow-up for survivors was 10.47 (range 0.20-45.80) months. A logistic regression model accurately predicted neurotoxicity (AUC: 0.830), and Cox proportional-hazards models for CAR-T response at 3 and 6 months demonstrated high accuracy (AUC: 0.754 and 0.818, respectively). Median predicted OS after CAR-T therapy was 4.73 months for high MTV_total and 37.55 months for low MTV_total. Median predicted PFS was 2.73 months for high MTV_total and 11.83 months for low MTV_total. For all outcomes, predictive models, combining imaging features and clinical variables, showed improved accuracy compared to models using only clinical variables or imaging features alone.

Conclusion: This study successfully integrates imaging features and clinical variables to predict outcomes in R/R B-cell lymphoma patients undergoing CAR-T. Notably, the identified MTV_total cut-off effectively stratifies patients, as evidenced by significant differences in OS and PFS. Additionally, the predictive models for neurotoxicity and CAR-T response show promising accuracy. This comprehensive approach holds promise for risk stratification and personalized treatment strategies which may become a helpful tool for optimizing CAR-T outcomes in R/R lymphoma patients.

Background: The introduction of quantitative SPECT/CT allows more objective assessments of tracer accumulation in SPECT. However standardized uptake values (SUV) still do not play a big role for orthopedic or oncologic questions. With a more reliable normalization, the use of quantitative measures might also be of use for a more objective assessment of lesions. We retrospectively included patients that received a quantitative [^99mTc]-HDP bone SPECT/CT scan of the lumbar spine for 4 body weight (BW) categories. Measurements of bone activity (kBq/cc) and bone density in Hounsfield Units (HU) in a standard volume of interest in the femur, the first and the fifth lumbar vertebra of all patients, without active disease within these regions was made. Correlations between tracer uptake and clinical parameters (BW, height, age, gender) were assessed with a multiple regression and based on the model coefficients, a correction formula was calculated and applied.

Results: The strongest correlation between measured activity in L1 and patient parameters was found for BW (r= -0.64, p < 0.001), compared to height (r = -0.28, p = 0.002) and age (r = -0.34, p = 0.001). Furthermore, there was a weak positive correlation between tracer accumulation and bone density (r: 0.35, p < 0.001). Using standard normalization with BW there was a very weak positive correlation between SUV_BW at L1 and BW with a slight overestimation in heavier subjects (r = 0.15, p = 0.09). The calculated correction based on the multiple regression of activity as dependent variable, and weight, age and bone density as significant predictors resulted in more robust uptake values with non-significant associations to BW, height, age or density. However, there was still a wide interindividual range of values for normalized bone activity.

Conclusion: Using an age, bone density and weight-based normalization significantly decreased the interindividual variability of normal uptake on quantitative SPECT/CT compared to the regularly used BW adjusted SUV_BW. However, a generalized normalization is difficult in the presence of strong patient effects, not attributable to the measured clinical variables.

Background: Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extracted from brown algae with nanomolar affinity for P-selectin. This first-in-human study evaluated in healthy volunteers the safety, whole-body biodistribution, and dosimetry of ^99mTc-fucoidan (Good Manufacturing Practices grade). We also investigated whether we could observe binding of ^99mTc-fucoidan to human thrombi ex vivo and in vivo. In ten healthy volunteers, conjugate whole-body scans were performed up to 24 h following intravenous injection of ^99mTc-fucoidan (370 MBq). Moreover, ^99mTc-fucoidan uptake in ex vivo human thrombi (n = 11) was measured by gamma counting. Additionally, three patients with a newly diagnosed deep vein thrombosis (DVT) were subjected to ^99mTc-fucoidan SPECT/CT imaging.

Results: ^99mTc-fucoidan was well tolerated in all participants without any drug-related adverse events. The total-body absorbed dose in males was comparable to females (0.012 ± 0.004 vs. 0.011 ± 0.005 mSv/MBq; p = 0.97). Gamma counting experiments demonstrated binding of tracer to ex vivo human thrombi that was 16% lower after blocking with a natural P-selectin ligand, Sialyl Lewis X. ^99mTc-fucoidan demonstrated specific uptake at the thrombus site in one out of three scanned patients with DVT.

Conclusions: ^99mTc-Fucoidan has a favorable biodistribution and safety profile. ^99mTc-fucoidan exhibited specific binding to human thrombi in both in vivo and ex vivo settings. Nonetheless, the in vivo results do not support further clinical investigation of ^99mTc-fucoidan as an imaging modality for DVT. Other clinical implementations of a technetium- 99m-labeled P-selectin tracer should be considered.

Trial registration: Clinicaltrials,NCT03422055.Registered 01/15/2018. URL: https://clinicaltrials.gov/study/NCT03422055 Landelijk Trial Register, NL7739. Registered 4/2/2019 . https://onderzoekmetmensen.nl/en/trial/26785.

Background: Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs. Data from 37 patients enrolled in a prospective phase II study (LuMEn) were analysed. Treatment consisted of four cycles of [¹⁷⁷Lu]Lu-DOTA-TATE administered 8-12 weeks apart. Three-time-point SPECT/CT imaging was performed after each treatment cycle, and dosimetry of tumours and organs-at-risk (kidneys and red marrow) was conducted following the medical internal radiation dose formalism. Coefficients of variation (CoV) assessed the variability of absorbed doses, activity concentrations on day 1, and effective half-lives. Linear mixed effect models (SAS software) were used to investigate the evolution of the dosimetric parameters over cycles, discerning between different primary NET types and grades of tumours.

Results: There is an important variability in absorbed doses and activity concentrations among patients, particularly in tumours (CoV: ~50%). Tumour absorbed doses and activity concentrations decreased over treatment cycles in pancreatic NETs, although at a limited rate (~-13%/cycle). An opposite trend was observed for the kidneys ( ~ + 8%/cycle). Effective half-lives remained relatively constant across cycles for both organs-at-risk and tumours. The primary NET type significantly influenced effective half-lives in tumours, shorter in pancreatic NETs than intestinal NETs (77 h vs. 107 h, p < 0.0001). No significant effect of the grade was observed on either of the variables investigated.

Conclusions: Our study revealed considerable variations in tumour absorbed doses among patients with NETs treated with a standardized protocol. These findings confirm the need for personalized dosimetry approaches in PRRT, considering patient and tumour characteristics.

Trial registration: EudraCT Number: 2012-003666-41.

Clinicaltrials: gov identifier: NCT01842165. Registered 25 April 2013, https://clinicaltrials.gov/ct2/show/NCT01842165 .

Background: Early evaluation of radiation sensitivity in lung cancer patients can facilitate the transition to personalized treatment strategies. To this end, we assessed the capability of ⁸⁹Zr-anti-γH2AX-TAT microPET imaging in determining the radiosensitivity of lung cancer xenograft models. We prepared and conducted quality control on ⁸⁹Zr-anti-γH2AX-TAT. The radiosensitivity of human non-small cell lung cancer cells (H460) and adenocarcinoma cells (A549) was analyzed through clonogenic survival experiments. Additionally, the role of γH2AX as a biomarker for radiosensitivity was validated by quantifying γH2AX foci via fluorescence staining. Subsequently, the H460 and A549 xenograft mouse models were subjected to irradiation, followed by ⁸⁹Zr-anti-γH2AX-TAT microPET imaging. Concurrently, we performed immunofluorescence staining for γH2AX in tumor tissues to establish a correlation between the uptake of ⁸⁹Zr-anti-γH2AX-TAT and γH2AX expression.

Results: The surviving fraction 2 Gy (SF2) values of H460 and A549 indicating that A549 adenocarcinoma has higher radiosensitivity. The cell immunofluorescence experiment showed that the repair of γH2AX foci in H460 cells after irradiation was significantly higher than that in A549 cells, which also confirmed that A549 has higher radiosensitivity. The microPET imaging results showed the uptake of ⁸⁹Zr-anti-γH2AX-TAT in the tumor of the A549 models after radiotherapy was higher than H460 models. The immunofluorescence staining of tumor tissue confirmed that the expression level of γH2AX was higher and the correlation with microPET imaging uptake was good.

Conclusion: ⁸⁹Zr-anti-γH2AX-TAT allows PET imaging of radiosensitivity in lung cancer xenograft models, and is expected to become an early evaluation method for lung cancer radiosensitivity.

Background: Primary mesenchymal tumors of the prostate are very rare, and there is no systematic report on fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT). The aim of this research was to characterize mesenchymal tumors of the prostate on ¹⁸F-FDG PET/CT.

Results: We included 13 patients with pathologically confirmed mesenchymal neoplasms of the prostate. The location, size, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total glycolysis of the lesion (TLG), pathologic findings, and available imaging study of the tumors were reviewed. Of the 13 patients (median age, 38 years; ranged from 13 to 74 years), the mean size of the tumors was 8.8 cm in diameter ranged from 5 to 16.1 cm. SUVmax ranged from 3.1 to 17.6 (mean 9.5), MTV ranged from 4.9 to 398 cm³ (mean 109 cm³) and TLG ranged from 21.3 to 1216 g (mean 96 g). The seminal vesicles, rectum, and bladder are the most commonly affected sites of invasion, while metastasis typically occurs in the bones, lungs, and lymph nodes.

Conclusions: Mesenchymal tumors of the prostate revealed large sizes and high SUVmax, MTV and TLG levels on ¹⁸F-FDG PET/CT. ¹⁸F-FDG PET/CT may be useful for accurate diagnosis, staging, and restaging, which plays an important role in the management of subsequent plans.

Background: Heart-type fatty acid binding proteins (FABP3) constitute a family of lipid chaperone proteins. They are found in the cytosol and enhance cellular fatty acid solubilisation, transport, and metabolism. FABP3 is highly expressed in the myocardium and is released from myocytes during myocardial damage. As FABP3 content in the myocardium is closely related to the metabolic state of fatty acids, we hypothesised that targeting of FABP3 with a radiolabelled small organic compound would visualise myocardium.

Results: The selective FABP3 inhibitor, 4-(4-fluoro-2-(1-phenyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)phenoxy)butanoic acid (LUF), was radiolabelled via a two-step reaction comprising copper-mediated ¹⁸F-fluorination of an arylboronic precursor followed by alkaline hydrolysis of the ethoxy protecting group. [¹⁸F]LUF was successfully synthesised by automated synthesiser with sufficient activity yields (14.0 ± 1.8 GBq) and high quality (molar activity, > 250 GBq/µmol and radiochemical purity, > 99.6%). Biological assessment of [¹⁸F]LUF as an in vivo myocardial imaging agent included evaluations of biodistribution, metabolite analysis, and positron emission tomography (PET) imaging of small animals. [¹⁸F]LUF clearly visualised the myocardium with high contrast against background tissues such as the lung and liver. [¹⁸F]LUF also showed a high absolute myocardial uptake equivalent to that of the promising myocardial perfusion tracer [¹⁸F]flurpiridaz and excellent metabolic stability in the body. These properties are ideal for stable and noise-less imaging of the heart. PET imaging of rat surgical permanent myocardial infarction (MI) and experimental autoimmune myocarditis (EAM) was also performed. [¹⁸F]LUF successfully visualised lesions of permanent MI and EAM.

Conclusion: Our results showed for the first time that the ¹⁸F-labelled FABP3 selective small organic compound clearly visualised myocardium with good quality. To determine the clinical utility of [¹⁸F]LUF for cardiovascular disease in clinical practice, it will be necessary to evaluate a greater variety of cardiovascular disease models and elucidate the accumulation mechanism, particularly in relation to fatty acid metabolism in the myocardium.

Background: A considerable portion of patients with fever of unknown origin (FUO) present concomitant lymphadenopathy. Diseases within the spectrum of FUO accompanied by lymphadenopathy include lymphoma, infections, and rheumatic diseases. Particularly, lymphoma has emerged as the most prevalent etiology of FUO with associated lymphadenopathy. Distinguishing between benign and malignant lymph node lesions is a major challenge for physicians and an urgent clinical concern for patients. However, conventional imaging techniques, including PET/CT, often have difficulty accurately distinguishing between malignant and benign lymph node lesions. This study utilizes PET/CT radiomics to differentiate between lymphoma and benign lymph node lesions in patients with FUO, aiming to improve diagnostic accuracy.

Results: Data were collected from 204 patients who underwent ¹⁸F-FDG PET/CT examinations for FUO, including 114 lymphoma patients and 90 patients with benign lymph node lesions. Patients were randomly divided into training and testing groups at a ratio of 7:3. A total of 15 effective features were obtained by the least absolute shrinkage and selection operator (LASSO) algorithm. Machine learning models were constructed using logistic regression (LR), support vector machine (SVM), random forest (RF), and k-nearest neighbors (KNN) algorithms. In the training group, the area under the curve (AUC) values for predicting lymphoma and benign cases by LR, SVM, RF, and KNN models were 0.936, 0.930, 0.998, and 0.938, respectively. There were statistically significant differences in AUC between the RF and other models (all P < 0.001). In the testing group, the AUC values for the four models were 0.860, 0.866, 0.915, and 0.891, respectively, with no statistically significant differences observed among them (all P > 0.05). The decision curve analysis (DCA) curves of the RF model outperformed those of the other three models in both the training and testing groups.

Conclusions: PET/CT radiomics demonstrated promising performance in discriminating lymphoma from benign lymph node lesions in patients with FUO, with the RF model showing the best performance.