Sarcoidosis is an inflammatory granulomatous disease of unknown cause, and cardiac sarcoidosis (CS) is the main cause of death in patients with sarcoidosis. Cardiac 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used to detect active CS, based on the patterns of 18F-FDG uptake in the myocardium. In this study, we investigated the ability of a model observer, Channelized Hoteling Observer (CHO), in differentiating the active CS pattern, in comparison with the diagnosis by the expert cardiac nuclear medicine (NM) physician as a reference standard. This retrospective study included 223 patients who underwent 18F-FDG PET scans because they were clinically suspected of having CS. One expert cardiac NM physician and one oncology NM physician classified the cardiac 18F-FDG uptake into four patterns (focal, focal on diffuse, diffuse, none) for all PET images. The oncology NM physician additionally determined the confidence scale of CS expressed as a percentage (0-100). The focal and focal on diffuse patterns were defined as CS patterns. In CHO, 80 subjects (CS: 40, non-CS: 40) were used for training data sets, and 143 subjects (CS: 66, non-CS: 77) were used for evaluation data sets of objective CS discrimination ability, respectively. The confidence scale of CS by CHO was also output as a percentage (0-100). Finally, ROC analysis was used to compare discrimination ability between the oncology NM physician and CHO by refereeing the classification of the cardiac NM physician as a standard. The match rate of classified subject numbers between the two physicians was moderate (Kappa coefficient of 0.57). In comparison with the judgment of the expert cardiac NM physician, the area under the ROC curve of oncology NM medicine and that of CHO were 0.73 and 0.78, respectively. The detection ability of CHO in CS pattern of myocardial 18F-FDG uptake was almost equivalent to that of the oncology NM physician when the diagnosis by the cardiac expert NM physician was defined as a reference standard. Even though the reference standard is not made by Japanese Circulation Society guidelines, the model observer has a potential alternative for assessing the discrimination ability of 18F-FDG uptake patterns of CS.
BACKGROUND AND OBJECTIVE: The diagnosis of infectious diseases is often a challenging problem faced by clinicians, especially in the case of complex infections manifested as fever of unknown origin or inflammation of unknown origin (FUO/IUO). Currently, 18F-fluorodeoxyglucose (FDG) Positron emission tomography/Computed tomography (PET/CT) has been increasingly used in the inflammatory diseases. This study aimed to explore the diagnostic and therapeutic value of FDG PET/CT for infectious diseases in patients with FUO/IUO. METHODOLOGY: A retrospective analysis was conducted on the clinical and imaging data of 156 consecutive hospitalized patients who underwent FDG PET/CT examination due to the etiological diagnosis of FUO/IUO and were ultimately diagnosed with infectious diseases. The analysis included general clinical characteristics and pathogenic distribution among patients. FDG PET/CT imaging results were evaluated, encompassing overall lesion detection rates in the cohort, detection efficacy for infectious foci caused by different types of pathogens, and FDG uptake patterns in lesions. The correlation between FDG PET/CT findings and serum inflammatory markers was assessed. Additionally, the impact of FDG PET/CT results on clinical diagnosis and treatment was evaluated through clinical questionnaires. RESULTS: Among the 156 patients with infectious diseases, 82 cases (52.6%) obtained etiological evidence, including 51 cases of bacterial infection, 13 cases of viral infection, 5 cases of other rare pathogens infection, and 13 cases of mixed infection. The remaining 74 cases without pathogen evidence were confirmed to be effective in antimicrobial therapy through clinical follow-up. In FDG PET/CT imaging, abnormal FDG uptake was observed in 139 cases (89.1%), among which infection foci were detected in 100 cases (64.1%). The detection rate of mixed pathogen infection lesions by FDG PET/CT was significantly higher than that of viral infection lesions (χ2 = 6.500; P = 0.011). Infections with different types of pathogens could involve multiple organs and tissues throughout the body, and there was no significant difference in the distribution of infection foci. There was no significant difference in the degree of FDG uptake in infection foci, liver, spleen, and bone marrow among different types of pathogens. There were statistical differences in the levels of serum CRP, WBC, NE%, NEUT#, LY%, LYMP# and LDH among the patients with detected infection foci by FDG PET/CT, patients manifested as non-specific inflammatory uptake, and patients with negative PET/CT (all P < 0.05). Clinical questionnaire results showed that FDG PET/CT was helpful in the initial etiological diagnosis for 100 patients (64.1%); 33 patients (21.2%) obtained etiological evidence through biopsy at the site indicated by PET/CT; and the treatment plan was changed after FDG PET/CT examination in 68 patients (43.6%). CONCLUSION: For complex infectious diseases in FUO/IUO, FDG PET/CT can not only help detect infectious foci, indicate appropriate biopsy sites and assist in obtaining etiological evidence, but also provide key information for the establishment of clinical treatment plans.
Recent progress in nuclear medicine has been driven by continuous advances in radiotracers, imaging technologies, and radiopharmaceutical therapies, leading to an expansion of clinical applications supported by an increasing body of evidence. In particular, systematic reviews and meta-analyses have played an important role in quantitatively evaluating the clinical value of these developments. This narrative review provides an overview of recent meta-analytic evidence in nuclear medicine, with a primary focus on oncologic applications, while briefly addressing developments in cardiology and neurology. In oncology, positron emission tomography (PET)/computed tomography (CT) using fluorodeoxyglucose (FDG) has become an established imaging modality for post-treatment assessment across various malignancies. Meta-analyses indicate that volumetric metabolic parameters, such as metabolic tumor volume and total lesion glycolysis, are more consistently associated with clinical outcomes than conventional single-voxel metrics. In addition, the interim and post-therapy metabolic response, assessed by FDG PET/CT, provides clinically relevant prognostic information and may contribute to treatment monitoring. Beyond FDG, tumor-targeted PET tracers, including prostate-specific membrane antigen and somatostatin receptor ligands, have demonstrated improved diagnostic performance in specific malignancies, and emerging tracers such as fibroblast activation protein inhibitors represent promising future directions. Radiopharmaceutical therapy has also shown notable progress, with meta-analytic evidence supporting the effectiveness and acceptable safety of peptide receptor radionuclide therapy for neuroendocrine tumors, as well as for advanced prostate cancer. In nuclear cardiology and neurology, advances in PET and single photon emission CT technologies have enabled more precise disease characterization, although their clinical roles continue to evolve. Overall, accumulating meta-analytic evidence supports the growing clinical importance of nuclear medicine. Continued methodological refinement and further evidence generation will be essential to optimize patient management in routine clinical practice.
OBJECTIVE: Targeted radionuclide therapy (TRT) requires patient-specific dosimetry to optimize treatment efficacy while reducing toxicity. A RadioTherapy package based on PHITS (RT-PHITS) is a full Monte Carlo (MC) simulation-based dose calculation platform. This platform enables individualized 3D dose assessment using single photon emission computed tomography (SPECT)/computed tomography (CT) images of patients who undergo TRT with the peptide receptor DOTATATE labeled with 177Lutetium (177Lu). The present study aimed to investigate the influence of uncertainties arising from the limited number of histories in MC simulation, the integration range of time-activity curves (TACs), and the numbers of imaging time points on the accuracy of dosimetry based on MC simulation. METHODS: SPECT/CT images acquired at multiple time points from two patients (Patients A and B) treated with 177Lu-DOTATATE in the 177Lu Dosimetry Challenge dataset were used for dosimetry analysis. Absorbed dose calculations were performed using the Monte Carlo–based dosimetry software RT-PHITS and an in-house dosimetry system. We then evaluated the dependence of statistical uncertainty on the total number of simulated particles and on a newly defined index–the volume-normalized histories for each lesion and organs at risk (OAR) in the MC simulation. Absorbed doses for lesions and OARs were calculated under a TAC integration range of 124–9,999 h. Reduced datasets at three and two time points were also analyzed. RESULTS: Accuracy was reliable when 107 histories were achieved under our simulation conditions, although the optimal number of histories largely depends on total source volume and target size. In contrast, the coefficients of variation of calculated absorbed doses versus the volume-normalized histories were consistent across all lesions and OARs. Lesion dose estimates increased with longer TAC integration, whereas kidney doses reached a plateau > 300 h. Absorbed doses estimated based on three imaging time points were generally within approximately ± 10% of those obtained using four time points for most evaluated lesions and OARs, whereas the use of two time points resulted in larger deviations. CONCLUSION: Accurate 177Lu-DOTATATE dosimetry with RT-PHITS requires careful selection of TAC range and number of histories, particularly for lesion dose estimation.
The success of surgical treatment in Primary Hyperparathyroidism (PHPT) depends on the accurate localization of the parathyroid adenoma. Although cervical ultrasonography (USI) and ⁹⁹ᵐTc- Sestamibi scintigraphy are common methods in this context, their diagnostic performance might be limited in small, ectopically located, or biologically atypical lesions. As a novel PET agent targeting integrin αvβ6 (alpha-v beta-6), ⁶⁸Ga-Trivehexin can image biological processes associated with pathological tissue remodeling. This proof-of-concept study aimed to evaluate the feasibility and potential diagnostic contribution of ⁶⁸Ga-Trivehexin PET/CT in detecting parathyroid adenoma in patients with PHPT. This single-center, prospective proof-of-concept study included 28 patients who had a biochemical diagnosis of PHPT. All patients underwent neck ultrasound, ⁹⁹ᵐTc-Sestamibi parathyroid scintigraphy, and ⁶⁸Ga-Trivehexin PET/CT imaging. Fine Needle Aspiration Biopsy (FNAB) and Parathyroid Hormone (PTH) washout tests were performed for some patients as clinically necessary. Histopathological findings were used as the reference standard in patients who underwent surgery. The agreement between imaging methods was evaluated with Cohen's Kappa coefficient for exploratory purposes. A total of 64.2% of the patients were female, and the mean age was 56.1 ± 11.3 years. ⁹⁹ᵐTc- Sestamibi scintigraphy was found to be positive in 60.7% of the patients, while the positivity rate for ⁶⁸Ga-Trivehexin PET/CT was 78.6%. A significant proportion of cases with negative ⁹⁹ᵐTc- Sestamibi scintigraphy showed positive lesions with ⁶⁸Ga-Trivehexin PET/CT. Statistically significant, moderate agreement levels were detected in all patients between ⁹⁹ᵐTc-Sestamibi scintigraphy and ⁶⁸Ga-Trivehexin PET/CT (kappa = 0.430; p = 0.013). A moderate level of agreement was observed between the two methods in patients with histopathologically confirmed parathyroid adenoma (kappa = 0.429; p = 0.070). The results of this proof-of-concept study imply that ⁶⁸Ga-Trivehexin PET/CT may be a feasible and promising imaging method for localizing parathyroid adenomas in patients with primary hyperparathyroidism. It may offer potential contributions as a complementary diagnostic tool, particularly in selected cases where conventional imaging methods are limited. Further large, multicenter studies are needed to confirm these findings.
The aim of this study was to evaluate the diagnostic performance and lesion localization capability of [⁶⁸Ga]Ga-Trivehexin PET/CT for hyperfunctioning parathyroid tissue in primary hyperparathyroidism (P-HPT), through a retrospective analysis of data obtained from prospective studies conducted at two different centres, compared with the conventional preoperative imaging modalities [⁹⁹ᵐTc]Tc-MIBI scintigraphy and neck ultrasonography (US). A total of 44 patients diagnosed with P-HPT based on clinical and laboratory parameters, who subsequently underwent cervical ultrasonographic evaluation, were included in this study. For all patients, serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), 25-OH vitamin D, urea, creatinine, glomerular filtration rate (GFR), and 24-hour urinary calcium values were recorded. Following cervical US examination, all participants underwent [⁹⁹ᵐTc]Tc-MIBI scintigraphy as part of the routine preoperative work-up. Thereafter, to determine the diagnosis and localization of hyperfunctioning parathyroid tissue, [⁶⁸Ga]Ga-Trivehexin PET/CT imaging was performed. All [⁶⁸Ga]Ga-Trivehexin PET/CT data were visually assessed and quantitative measurements were obtained. [⁶⁸Ga]Ga-Trivehexin PET/CT findings were evaluated in conjunction with PTH wash-out results, postoperative biochemical response confirmation, and histopathological assessment. Forty-four patients with P-HPT (median age, 52 years; range, 24-73) were included. [⁶⁸Ga]Ga-Trivehexin PET/CT identified 37 hyperfunctioning parathyroid foci in 36 patients, corresponding to a patient-based detection rate of 81.8% (36/44). US and [⁹⁹ᵐTc]Tc-MIBI scintigraphy detected lesions in 45.5% (20/44) and 47.7% (21/44) of patients, respectively, while in the 4D-CT subgroup (n = 20), a lesion was detected in 13 patients. Among 23 [⁹⁹ᵐTc]Tc-MIBI-negative patients, [⁶⁸Ga]Ga-Trivehexin PET/CT demonstrated at least one positive focus in 18, and on a lesion-based analysis, [⁶⁸Ga]Ga-Trivehexin PET/CT confirmed 19 of 22 [⁹⁹ᵐTc]Tc-MIBI -positive lesions while revealing additional foci in [⁹⁹ᵐTc]Tc-MIBI-negative patients. According to the composite reference standard, [⁶⁸Ga]Ga-Trivehexin PET/CT achieved a sensitivity of 97.3% and a PPV of 100%, clearly outperforming [⁹⁹ᵐTc]Tc-MIBI scintigraphy and US. In patients with primary hyperparathyroidism, [⁶⁸Ga]Ga-Trivehexin PET/CT demonstrated significantly higher sensitivity than currently used standard imaging modalities. These findings suggest that [⁶⁸Ga]Ga-Trivehexin PET/CT represents a promising diagnostic alternative, particularly in cases where conventional imaging is negative or inconclusive.
Myocardial metabolism and perfusion in patients with ischemic heart disease or cardiomyopathy can be simultaneously assessed using 123I-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) and 201Thallium (Tl) dual-isotope images. However, cross-contaminated counts between these tracers complicate quantitative analyses, particularly of 123I-BMIPP washout rates (WRs). We developed a simplified method to determine WRs corrected for energy spectral crosstalk from dual-isotope images. Our correction method was based on fixed energy-spectrum spill-in ratios (iRatio for 123I and tRatio for 201Tl) that were empirically determined from phantom and patient datasets. These ratios were applied to separate 123I and 201Tl counts in 38 studies of 36 patients with ischemic heart disease using dual-energy planar and single-photon emission computed tomography (SPECT) images. We calculated WRs before and after correction using early and late anterior planar images, as well as mean tomographic counts derived from polar maps. Thresholds of 5% (planar) and 10% (SPECT) were used to assess classification agreement between corrected and uncorrected WRs. The range of iRatios was 0.57-0.73 and that of tRatios was 0.10-0.12. Higher iRatio values were associated with greater body-weight patients, whereas tRatios were relatively stable regardless of body weight. The corrected 123I-BMIPP WR depends primarily on tRatio and, by formulation, is not directly affected by iRatio. Using a fixed tRatio of 0.12, the correction method revealed strong correlations between corrected and uncorrected WRs for planar imaging (R² = 0.969, p < 0.0001) and SPECT (R² = 0.964, p < 0.0001). Corrected 123I-BMIPP WRs were comparable to uncorrected values for both planar imaging (mean difference, - 1.4%) and SPECT (mean difference, 0.8%). Among the 38 studies, classification of tentative normal versus abnormal WRs remained concordant in 35 (92%) planar studies and 36 (95%) SPECT studies. Our simplified energy spectrum-based method demonstrated that correction of 123I-BMIPP WRs is feasible under dual-isotope conditions. Although uncorrected WRs may provide approximate estimates, correction is important for reliable quantitative use of dual-isotope datasets, where spectral cross-talk limits accuracy. The proposed model-based approach improves the robustness and interpretability of WR assessment and enables practical, standardized quantitation.
In the new era of nuclear breast imaging, differentiating benign from malignant uptake in the breast is essential in guiding clinical management. Accordingly, we aimed to assess the pattern of PEM uptake in benign and malignant breast lesions and to investigate its correlation with different histopathological subtypes, histological tumor grades, and molecular subtypes. This was a prospective study comprised of 337 women with 465 breast lesions, of whom 128 patients had bilateral breast lesions. All patients performed Positron Emission Mammography (PEM) from March 2022 to February 2024. Any abnormality was evaluated qualitatively (mass and non-mass enhancement ) and quantitatively ( PUVmax and LTB ratio). The PEM readings were correlated with final pathology to differentiate benign from malignant lesions, and receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant ability of PUVmax and LTB ratio in distinguishing histopathological groups, histological grades, and molecular subtypes. According to the final pathology, 330 (71%) lesions were malignant, and 135 (29%) were benign. The ROC curve analysis showed cutoff values of 1.92 and 3.145 for PUVmax and the LTB ratio, respectively, to discriminate between benign and malignant breast lesions. Significant differences in PUVmax and LTB ratio were detected between benign lesions and histopathological types, grades, and molecular malignant subtypes. The cutoff values for PUVmax and LTB ratio from benign were 1.81 and 3.165 for Ductal carcinoma in situ, 2.09 and 3.55 for invasive duct carcinoma (IDC) 1.62 and 2.8 for invasive lobular carcinoma,1.92 & 3.165 for grade I, 1.935 & 3.145 for grade II & III tumors, 1.92 and 3.145 for luminal molecular subtype, 1.95 and 3.45 for HER 2 subtype, and 2.28 and 4.27 for the triple-negative subtype respectively. The lesions with irregular shapes, uncircumscribed margins, and segmental non-mass distribution have higher PUVmax and LTB ratios. PEM is a valuable imaging modality for distinguishing between benign and malignant breast lesions. PEM may enable stratification of malignant lesions by histopathological subtype, tumour grade, and molecular subtypes. The highest metabolic activity was observed in invasive duct carcinoma, grade III, and the triple-negative molecular subtype. Overall, PEM can provide in vivo evaluation of breast lesion metabolic activity, leading to better lesion characterization and individualized patient management. However, due to methodological constraints, subgroup sample size, and radiation exposure, PEM should be regarded as an adjunct to sonomammography rather than a primary screening imaging modality.
To assess the feasibility of estimating myocardial flow reserve (MFR) from static standardized uptake values (SUVs) derived using stress and rest 13N-ammonia positron emission tomography (PET) images acquired with a silicon photomultiplier-based PET/computed tomography (CT) system. The goal was to simplify MFR assessment by avoiding dynamic acquisition while maintaining diagnostic accuracy. We retrospectively included 121 consecutive patients who underwent 13N-ammonia PET myocardial perfusion imaging. The mean SUVs of the left and right ventricles were measured on transverse-axis slices corresponding to the largest cross-sectional area, and the stress-to-rest SUV ratio was calculated. A logarithmic transformation was applied to the MFR, and linear regression models between the log-transformed MFR and the stress-to-rest left ventricular-SUV ratio were developed using six-fold cross-validation across 121 patients. The predicted MFR values from the test folds were then combined to evaluate model performance across all patients with a comparable MFR distribution. Model performance was assessed using the root mean square error (RMSE) between the estimated and true MFR values, and the diagnostic performance for identifying MFRs < 2.0 by receiver operating characteristic (ROC) curve analysis with 95% confidence intervals. The RMSE of the predicted MFR calculated using the linear regression model was 0.39. Using an optimal cut-off value of 1.79 for the predicted MFR, the model achieved an area under the ROC curve of 0.89 (95% confidence interval: 0.83-0.95), with a sensitivity of 75% and a specificity of 88%. The proposed simplified SUV-based approach exhibited clinically acceptable error for MFR estimation and could effectively identify patients with an impaired MFR. This method may facilitate quantitative MFR assessment in clinical settings where dynamic PET protocols or dedicated software are not available, thereby broadening access to physiological evaluation of myocardial perfusion.
In positron emission tomography (PET)/magnetic resonance imaging (MRI), attenuation correction (AC) for PET of the head is achieved by MRI data to generate pseudo-computed tomography (CT) images. However, for the torso, AC becomes more challenging due to the complexity of separating bone components. Additionally, generating accurate MRI-based CT using deep learning poses significant difficulties for the chest, primarily because perfectly paired MRI and CT training data are hard to obtain owing to respiratory motion and body movements. We previously demonstrated that MRI-to-CT conversion can be achieved without deformation, even using unsupervised learning for zero echo time (ZTE) MRI and CT data from different individuals. Building on this foundation, our study aims to apply this approach to AC in chest PET/MRI and assess their quantitative accuracy, reproducibility, and external validity. The datasets used included (1) training dataset (unpaired ZTE MRI and CT of PET/CT, n = 360 and 500, respectively); (2) test dataset (paired PET/MRI and PET/CT, n = 25 and 25, respectively); (3) repeatability assessment dataset (repeated PET/MRI, n = 15 × 2 scans for the same patient); and (4) external validation dataset (paired MRI component of PET/MRI and CT, n = 30 and 30, respectively, acquired at another institution). Unpaired training data were used to train the deep learning model of pseudo-CT generation from ZTE. The accuracy, repeatability, and reproducibility of the PET/MRI scans using ZTE- and deep learning-based AC (MRACZTE) were evaluated based on the similarity of the histograms and the mean standardized uptake value (SUVmean) of physiological background of bone and liver. The histogram correlation coefficients between MRACZTE and the AC map based on the CT (CTAC) for the spine were significantly higher than those between conventional AC (MRACDixon) and CTAC. Additionally, bone SUVmean obtained using MRACZTE showed reduced bias relative to CTAC compared with MRACDixon. This method proved to be reproducible on each patient level and robust against external validation. Unsupervised learning with unpaired ZTE and CT data enabled pseudo-CT generation with bone components that closely matched CT-based attenuation maps. Integration into MR-based attenuation correction resulted in stable physiological uptake measurements in chest PET/MRI, supporting the feasibility of this approach.
The rapid global expansion of targeted radionuclide therapy using 177Lu-labeled radiopharmaceuticals has increased the need for effective and regulatory-compliant management of radioactive wastewater. However, long-lived impurities, such as 177mLu, which emit high-energy γ-ray emissions complicate wastewater treatment and compliance with discharge regulations. This study aimed to determine an optimal method to treat wastewater contaminated with 177Lu and 177mLu. Radioactive wastewater samples were collected from a storage tank in a targeted radionuclide therapy ward. The adsorption efficiency of various adsorbents, including Chelex resin, Bondesil-C18 and granular activated carbon, was assessed using both batch and column methods. Adsorption efficiency was measured as counts at 208 keV using a high-purity germanium detector. The adsorption efficiency of Chelex resin and Bondesil-C18 in 100 mL of radioactive wastewater, was below 25%, whereas that of granular activated carbon was 85.9%. The adsorption efficiency of batch and column methods increased with adsorbent mass and processing time. The column method with small amounts of granular activated carbon achieved 60%-70% adsorption efficiency within ~ 7 min in a single-pass operation. Adsorption treatment using granular activated carbon was effective for the removal of 177Lu and 177mLu from radioactive wastewater. Column method may support the management of radioactive wastewater contaminated with 177Lu and other radionuclides in clinical settings.
OBJECTIVE: 15O-gas positron emission tomography (PET), which enables quantitative assessment of cerebral blood flow and oxygen metabolism, is widely performed to diagnose cerebrovascular disorders and evaluate therapeutic effects. While the autoradiography method offers high quantitative accuracy, short restraint time, and reduced radiation exposure as advantages over the steady-state method, it requires several radiation detectors in addition to a PET scanner. In contrast, PET/CT systems optimized for whole-body tumor imaging with 18F-2-deoxy-2-fluoro-D-glucose have high sensitivity, and recent regulatory developments have facilitated active efforts to reduce radiation dose through low-dose administration. Dose reduction is desirable for 15O-gas PET, which involves the inhalation of relatively high radioactivity concentrations; nonetheless, obtaining an arterial input function with sufficient statistical precision is challenging under low-dose conditions. In this study, we aimed to investigate how variations in the crosscalibration factor between the dose calibrator and the continuous blood-sampling system (CCFcbs), as well as the magnitude of statistical noise in the arterial input function measured using the continuous blood-sampling system (aTACnoise), affect the quantitative parameters of cerebral blood flow and oxygen metabolism images. METHODS: Ten patients with cerebrovascular disease (six men and four women) with a median age of 61.5 years were enrolled. The effects of CCFcbs and aTACnoise on quantitative cerebral hemodynamic and metabolic parameters were evaluated. RESULTS: Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) showed an inverse correlation with CCFcbs; however, the oxygen extraction fraction (OEF) was minimally affected. aTACnoise had a greater impact on OEF and CMRO2 than on CBF, and the variability increased as statistical precision decreased. CONCLUSIONS: A highly sensitive continuous blood-sampling system or technical improvements that enable higher-sensitivity measurements are crucial for obtaining an arterial input function with sufficient statistical precision. Furthermore, standardization of the calibration procedure is essential.
Bone scan indexes (BSIs) are frequently applied in Japan, Europe and the USA. The BONENAVI (Japan) and aBSI (Europe and USA) software programs were developed based on different training and validation datasets to calculate BSIs. However, whether they are compatible has not been systematically determined. We compared BSIs generated by these programs in a patient cohort to clarify correlations between them. We retrospectively analyzed 339 scintigraphic data from 34 patients (mean age, 69.9 ± 9.1 [48-89] y) with prostate cancer who underwent whole-body bone scintigraphy to evaluate metastatic bone disease. Anterior and posterior whole-body scans with 99mTc-methylene-diphosphonate (MDP) were processed then BSIs were computed by aBSI and BONENAVI. Systematic differences between aBSI and BONENAVI were evaluated using Pearson's correlation coefficients and Bland-Altman analysis. We also categorized BSIs during follow-up as decreased, unchanged, or increased, and evaluated agreement between longitudinal changes. The mean number of bone scans per patient was 10.0 ± 6.8 (1-26), and longitudinal changes in BSIs were evaluated using 305 pairs of follow-up studies. The automatic BSIs from aBSI and BONENAVI were 3.23% ± 3.47% and 2.91% ± 2.84%, respectively. Both strongly correlated (r = 0.947, p < 0.001). Bland-Altman plots revealed that aBSI tended to yield slightly higher BSIs (mean difference, + 0.31% (95% CI, 0.19-0.44, p < 0.001). A subgroup analysis of BSIs > 7% revealed higher automatic BSIs from aBSI than BONENAVI (mean difference, + 1.57%; 95% CI, 0.99-2.15; p < 0.001). The rate of longitudinal changes in BSI during follow-up substantially agreed (78.7% vs. 76.4% with respective thresholds of ± 0.5% and ± 0.3% (κ = 0.63, Cramer's V = 0.65, p < 0.0001 for both). The aBSI and BONENAVI BSIs computed by the software programs strongly correlated and longitudinal changes during follow-up studies generally concurred. However, BSIs from aBSI tended to be higher among patients with an increased disease burden compared with BONENAVI. Clinicians and investigators should be aware of these differences when interpreting or comparing results among software programs.
OBJECTIVE: The present study aims to assess the performance of a CT-guided spatial normalization method (CT-method) for the anatomical region-of-interest (ROI)-based semi-quantification of dopamine transporter (DAT) single photon emission computed tomography (SPECT) images and the detection of nigrostriatal degeneration as compared to an effective SPECT template-based method (MSPECT-method) and visual analysis performed by an expert reader. METHODS: Patients who underwent [123I]FP-CIT SPECT/CT in the Hospices Civils de Lyon between 2008 and 2018 for clinically uncertain parkinsonian syndromes were included. The proposed CT-method aimed to spatially normalize the jointly acquired CT scans and apply the deformation fields to the coregistered SPECT images. It was compared to an effective SPECT template-based method using multiple templates as target for the spatial normalization (MSPECT-method). The distribution of specific binding ratios (SBR) was compared between both methods and the SBR classifications were compared to an expert’s visual classification of the scans, which served as the reference. RESULTS: Overall, 1156 patients (mean age ± SD = 68.7 ± 11.5; 52.6% male) were included. The CT-method provided a good separation between the normal and reduced SBR, with a higher effect size of the distance between the Gaussians (3.31 vs 3.11) and smaller overlap (6.44% vs 8.96%) compared to the MSPECT-method. Both the CT-method and MSPECT-method demonstrated high classification accuracy (96.7%, 95% CI: 95.7-97.7% vs. 94.6%, 95% CI: 93.3-95.9%), sensitivity (96.0%, CI: 94.3-97.7% vs. 89.7%, CI: 87.1-92.3%), and specificity (97.3%, CI: 96.1-98.6% vs. 98.7%, CI: 97.9-99.6%), respectively. CONCLUSIONS: The proposed CT-guided spatial normalization method for automated semi-quantitative [123I]FP-CIT SPECT analysis is a viable option when CT images are available. It offers objective spatial normalization and provides high accuracy for the detection of nigrostriatal degeneration, closely aligning with an expert’s visual interpretation.
Cardiac sarcoidosis (CS) is a potentially life-threatening condition, and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is highly sensitive for detecting myocardial inflammation. However, corticosteroid therapy may alter myocardial metabolism, complicating the interpretation of FDG PET. This study aimed to evaluate the impact of corticosteroid therapy on physiological myocardial FDG uptake and assess the utility of fasting plasma glucose (FPG) and free fatty acids (FFA) in distinguishing physiological from pathological uptake. We retrospectively analyzed FDG PET/CT scans of 40 CS patients who underwent paired scans before and after corticosteroid therapy, following prolonged fasting (> 18 h). The frequency of physiological myocardial FDG uptake was compared, and FPG and FFA levels were assessed as predictors using receiver operating characteristic (ROC) analysis. Exploratory analyses were also performed to assess metabolic changes across different levels of corticosteroid exposure. Physiological myocardial FDG uptake significantly increased after corticosteroid therapy (from 2.5% to 15%, P = 0.048). Post-treatment FFA levels were significantly lower, while FPG levels were higher. An FFA cutoff of 615 µEq/L predicted physiological uptake with 100% sensitivity and 83.6% specificity (AUC = 0.96, P < 0.001), whereas FPG showed poor discrimination (AUC = 0.43, P = 0.83). Patients with physiological uptake had significantly lower FFA levels; FPG did not differ between groups. In analyses stratified by corticosteroid dose, physiological uptake was less frequently observed at lower dose levels, accompanied by relatively preserved metabolic parameters. Corticosteroid therapy increases physiological myocardial FDG uptake in CS patients, likely due to reduced FFA levels and altered metabolism. FFA may serve as a useful marker for distinguishing physiological FDG uptake from abnormal uptake, supporting more accurate PET interpretation during corticosteroid therapy.
OBJECTIVE: Commercial Artificial Intelligence (AI) tools for [18F]FDG PET/CT lack real-world evidence. This study evaluated the lesion detection performance of two commercial AI-based algorithms, both alone and as adjuncts to expert reading. METHODS: We retrospectively analyzed 151 [18F]FDG PET/CT scans of patients managed for melanoma or lymphoma in 3 French centers. Lesion were detected by 4 methods: manual expert reading (M1); a PET Assisted Reporting System trained on 629 patients with lymphoma and lung cancers, with SUV 2.5 threshold (M2) or PERCIST-like threshold (M3), and a one-step U-net algorithm trained on 4,906 patients with multiple neoplasia (M4). Expert consensus adjudicated all volumes of interest (VOIs) as the lesion-level reference standard, with neoplastic VOIs designated as true positives (TP). Primary endpoint was per-lesion sensitivity. Secondary endpoints were false-positive (FP) VOIs, and performance of human–AI combinations. RESULTS: Among 1,544 reference lesions, per-lesion sensitivity was 76.6% (M1), 60.2% (M2), 44.3% (M3), 95.7% (M4), 83.4% (M1 + M2), 79.7% (M1 + M3), and 99.9% (M1 + M4). All methods combining AI and expert reading showed significantly higher sensitivity than that obtained by the expert alone. Higher sensitivity coincided with greater false-positive burdens: FP VOIs were 837 (M2), 151 (M3), and 1,435 (M4). Subgroup analyses showed human sensitivity dropped with > 5 lesions, while AI sensitivity was preserved. CONCLUSION: Our study of several commercially available software solutions reveals that deep learning algorithms are currently not accurate enough to be used without being combined with expert interpretation. The number of false positive VOIs was higher for solution offering the higher sensitivity, which may hinder their widespread use.
PURPOSE: Quantitative [11C]NNC112 PET imaging of dopamine D₁‑receptors conventionally requires 90–120 min of dynamic data, limiting workflow and patient comfort. In this study, we investigated how gradual scan duration shortening affects the calculation of non‑displaceable binding potential (BPND) of D1-receptors. METHODS: Fourteen healthy volunteers (26 ± 4 years) underwent 90‑minute dynamic [11C]NNC112 PET/MRI scans. BPND was calculated with the simplified reference‑tissue model (SRTM) using cerebellar grey matter as reference. Time‑stability analyses were performed on truncated datasets of 75, 60, and 45 min. Absolute (non-relative) bias, percent error, and Bland–Altman limits of agreement (LoA) were calculated for 10 cortical and striatal regions. Regression analyses were performed to analyze the relationships of bias with imaging duration. RESULTS: Reducing the acquisition to 75 min introduced a median absolute BPND bias of less than + 0.02 (+ 0.17% to + 2.19%) with a relatively acceptable LoA (− 2.88% to + 12.6%; <10% in all regions except the frontal cortex). A 60-minute protocol remained relatively reliable in the high-binding striatum, with LoA values at or near ± 10% (− 7.06% to + 12.8% for the caudate and − 5.69% to + 10.33% for the putamen). However, significant deviations were observed in low-binding cortical regions. Truncation to 45 min consistently overestimated BPND values in both cortical and striatal regions and widened LoA significantly. CONCLUSION: Dynamic [11C]NNC112 PET/MRI can potentially be shortened to 75 min with acceptable whole-brain quantitative accuracy. A 60-minute protocol may be feasible for striatal-focused studies. However, 45-minute acquisitions had significant deviations and should be approached with caution for accurate D₁-receptor quantification with [11C]NNC112 PET imaging.
The introduction of prostate-specific membrane antigen-ligand positron emission tomography/computerised tomography (PSMA-ligand PET/CT) into clinical practice has altered the prevalence of non‑metastatic (by conventional imaging) castration-resistant prostate cancer (nmCRPC). We herewith briefly review the biochemical and imaging parameters in nmCRPC and mainly focus on decoding disease localization using PSMA- ligand PET. The effective restaging with more accurate PSMA PET-based disease identification and characterization potentially signifies the entrance of the nmCRPC stage in the twilight zone. Moreover, it seems plausible that the small fraction of the nmCRPC invisible even on PSMA PET may constitute a latent phase of occult growth of the tumor cells. Supposedly, triggering of PSMA overexpression on the PCa cells under androgen deprivation therapy (ADT) through certain anticancer or other therapies such as protein kinase inhibitors (PKIs), dutasteride, or cholesterol-lowering regimes, might further hasten visualisation of micrometastases on PSMA-ligand PET, eventually transforming the nmCRPC stage into a defined, potentially curable target.
Radioligand therapy (RLT) has expanded rapidly across oncology, yet it remains unclear whether this expansion reflects broad multi-target maturation or continued concentration within a limited number of clinically deployable target-defined platforms. We hypothesized that contemporary systemic solid-tumor RLT development remains concentrated in a small number of more consolidated platforms rather than representing diffuse multi-target maturation. This retrospective trial-level observational analysis used a prespecified Trialtrove export generated on March 23, 2026, restricted to Therapeutic Area = Oncology and Mechanism of Action = Radioemitter, with observational studies excluded. The raw export yielded 1341 oncology radioemitter trial records. Row-level platform-consistency curation excluded residual hematologic records, locoregional or intracavitary radiotherapies, non-targeted bone-seeking radiopharmaceuticals, and diagnostic-only studies, yielding a broad solid-tumor radioemitter universe of 558 trials. Additional exclusion of systemic radioligand records without a stably identifiable molecular target in the export fields produced a target-anchored systemic RLT universe of 513 trials. Future/planned records beyond 2025 were excluded from the historical main-text figure universe, leaving 462 trials. All eligible trials were included regardless of current status or achieved study phase; phase was used only as a descriptive grouping variable. Developmental consolidation was assessed descriptively across disease niche coherence, radionuclide strategy, scaffold architecture, and progression beyond early-phase exploration. PSMA (n = 179) and somatostatin receptor (SSTR; n = 128) together accounted for 307 of 462 historical trials (66.5%). Disease positioning remained strongly target-centered, with PSMA overwhelmingly prostate-focused and SSTR concentrated in neuroendocrine tumors. PSMA and SSTR showed marked Lu-177 predominance, whereas newer target families were more radionuclide-heterogeneous. SSTR was almost entirely peptide-based, whereas PSMA spanned small-molecule/ligand, peptide, and antibody/engineered-protein formats. Phase 2 or later development was reached by 44.7% of PSMA trials and 52.3% of SSTR trials, but by only 11.1% of FAP trials, none of GRPR trials, 30.0% of CAIX trials, and 16.4% of trials in the broader other-target group. Current systemic solid-tumor RLT development is characterized less by broad multi-target maturation than by marked platform concentration with uneven developmental consolidation. In this descriptive framework, trial growth alone is insufficient to indicate platform maturity; more informative is whether a target can sustain a coherent disease niche, a workable radionuclide strategy, a deployable carrier format, and advancement beyond early-phase exploration.
BACKGROUND: Scintigraphy using bone-avid tracers like 99mTc-diphosphono-propanodicarboxylic acid (99mTc-DPD), 99mTc-hydroxymethylene-diphosphonate (99mTc-HMDP), or 99mTc-pyrophosphate (99mTc-PYP) is a widely available and non-invasive imaging tool for diagnosis of cardiac amyloidosis. Visual evaluation and semi-quantitative image analyses reach excellent sensitivity and specificity results. For 99mTc-HMDP, high accuracy of early semi-quantitative parameters derived from imaging 10 min after tracer injection was described but never validated for other tracers. The aim of this study was to evaluate early semi-quantitative parameters in 99mTc-DPD scintigraphy. METHODS: 122 patients (78 male / 44 female) with suspected cardiac amyloidosis who underwent 99mTc-DPD scintigraphy were retrospectively analysed. Early and late planar whole-body scintigraphy images were acquired 10 min (+ 5 min) and 2.5–3.5 h after tracer injection. Early cardiac 99mTc-DPD uptake was evaluated using the Heart/whole-body rectangular (H/WBr), Heart/whole-body profile (H/WBp), Heart/Skull (H/S), Heart/Mediastinum (H/M), Heart/Contralateral Lung (H/CL), Heart/Liver (H/L), and Heart/Pelvis (H/P) ratios. RESULTS : H/L was not correlated to the other parameters.Best results for prediction of Perugini ≥1 were achieved for H/M (sensitivity 69.6%, specificity 84.4%, accuracy 77.5%), best results for prediction of ATTR-CA for H/L (sensitivity 65.9%, specificity 88.6%, accuracy 80.8%). Adding the H/L to other parameters increased accuracy and specificity (best results for H/L+H/S: accuracy 83.3%, sensitivity 63.4%, specificity 93.7% to predict CA). CONCLUSION : Previous results for99mTc-HMDP were not confirmed; diagnostic precision of early 99mTc-DPD is not sufficient to replace late imaging in clinical routine. Early H/L is a novel, independent, and specific parameter which may be added to imaging protocols to increase the accuracy in combination with other imaging biomarkers