Background To determine whether a single post-neoadjuvant therapy (NAT) fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) measurement and maximum standardized uptake value (SUVmax) can guide surgical selection in anatomically resectable (R) or borderline-resectable (BR) pancreatic ductal adenocarcinoma (PDAC). Limitations of morphologic CT due to NAT-induced changes require decision-time biomarkers reflecting residual tumor biology. Methods This international multi-center retrospective study analyzed 923 patients with R or BR PDAC who underwent NAT, preoperative FDG-PET/CT, and pancreatectomy. An outcome-based post-NAT SUVmax threshold of 4.0 was derived from a temporal derivation cohort (2017–2019; n=413) and validated without re-optimization in an independent cohort (2020–2021; n=510). The endpoints were overall survival (OS), recurrence-free survival (RFS), early recurrence within 6 months (ER6), and first-failure pattern. Results Post-NAT SUVmax ≥4.0 was independently associated with inferior OS (derivation HR 1.86, 95% confidence interval [CI] 1.40–2.45; validation HR 1.53, 95%CI 1.13–2.07). Combining SUVmax (≥4.0 vs. <4.0) with post-NAT carbohydrate antigen 19-9 (CA19-9, >37 vs. ≤37 U/mL) yielded clear stepwise separation of RFS and OS. SUVmax ≥4.0 modestly predicted ER6 (area under the curve [AUC] 0.65), while a “double-positive” rule (SUVmax ≥4.0 and CA19-9 >37 U/mL) increased specificity (0.83) with lower sensitivity (0.42), with 32% ER6 in this subgroup. A high SUVmax was associated with distant, but not margin-related failure. Conclusions A post-NAT SUVmax threshold of 4.0 defined a reproducible, single-time-point metabolic criterion that complemented CA19-9 level to enable biology-guided surgical selection in anatomically resectable PDAC.

Background:Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. Methods:This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). Results:During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. Conclusions:FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation.

Time-of-flight (ToF) in PET improves image quality by enhancing the signal-to-noise ratio, and recent deep learning (DL)-based ToF (DL-ToF) methods further enhance tumor visibility and reduce noise. This study quantitatively investigates the effects of DL-ToF on PET images using the thoracoabdominal phantom simulating human anatomy. Methods: The phantom, containing optimized radioactivity of 18F-FDG in each organ and tumor, was scanned using a BGO crystal PET/CT machine. Imaging was performed at 6 acquisition times (1, 1.5, 2, 3, 5, and 10 min), with PET images reconstructed using the low, middle, and high levels of DL-ToF and non-ToF. The SUVmean and SUVmax of each organ, lung, and liver tumors were measured for each acquisition time. Additionally, shape index maps were generated to assess pixel value changes and the impact of DL-ToF on image quality. Results: DL-ToF processing significantly improved tumor visibility and contrast, especially with the high-precision DL (HDL) model. For lung tumors, the [Formula: see text] increased from 3.72 (non-ToF) to 5.89 (HDL) at 10 min. Liver tumor [Formula: see text] also increased, with HDL yielding the highest [Formula: see text] (5.62). Shape index maps suggested that clearer tumor boundaries and enhanced contrast were obtained with high-precision DL-ToF. Clinical cases of lung and liver tumors demonstrated similar trends, with improved tumor delineation. Conclusion: DL-ToF can affect lesion visibility and image characteristics in a manner dependent on its processing level, underscoring the importance of understanding its behavior for clinical implementation.

This study evaluates organ doses from ¹⁸F-FDG whole-body PET-CT using the phantom–based software PARaDIM and patient image–based software RT-PHITS and compares with reference data from ICRP Publication 128. Absorbed dose coefficients (mGy/MBq) were calculated using ICRP Publication 145 mesh-type phantoms in PARaDIM and 20 patient datasets (10 male, 10 female) from ‘The Cancer Imaging Archives’ website in RT-PHITS. Organs were segmented in 3D Slicer, and dose coefficients were derived after physical decay correction of the resultant dose rates (mGy/s). The patient cohort (n = 20; 10 males, 10 females) had an average age of 52.1 years, height of 172.1 cm, weight of 76.65 kg, and total administered activity of 306.55 MBq. Absorbed dose coefficients from PARaDIM and RT-PHITS ranged from 0.01 to 0.07 mGy/MBq. RT-PHITS showed acceptable agreement with ICRP 128 and PARaDIM for most organs, except for the urinary bladder and heart wall. Standard deviations (SD) for RT-PHITS urinary bladder doses were 0.04 relative to ICRP 128 and 0.12 relative to PARaDIM; heart wall SDs were 0.016 and 0.014, respectively. Overall, RT-PHITS organ doses yielded an average SD of 0.0073, with the highest deviation in the heart wall. The results indicate that anatomical differences lead to measurable variations between the generalized and individualized dosimetry methodologies. Because a consistent physical decay model of 18F was used, these variations primarily reflect structural and geometric factors. This study provides a framework for advancing individualized dosimetry approaches and supports future developments in cumulative exposure assessments and potential theranostic applications.

In Lu-177-labeled peptide receptor radionuclide therapy, dosimetry has recently gained importance for assessing side effects and treatment responses. However, no standard method has been established yet. In this retrospective study, we compared the kidney-absorbed doses of 24 treatments with Lu-177-DOTATATE using three methods: a planar method using only planar images, a hybrid method using planar and SPECT/CT images, and a SPECT/CT method using only SPECT/CT images. In the Planar method, the ROI was defined from 2D whole-body planar images and calculated using the MIRD method. In the Hybrid method, the VOI was defined from CT images and the VOIs were placed in the 2D planar image as ROIs, which were calculated using the MIRD method. For the SPECT/CT method, the VOI was defined from CT images and the mean absorbed dose was estimated on a voxel basis. The absorbed dose estimated with the Planar method (15.2 ± 5.81 Gy) was significantly higher than the estimates with the other two methods (Hybrid: 2.93 ± 1.33 Gy, SPECT/CT: 3.81 ± 0.93 Gy) (p < 0.05). The Hybrid and SPECT/CT methods exhibited the strongest correlation. The Planar method demonstrated the highest variability in estimated values. The use of 2D planar images alone tended to overestimate the absorbed dose compared to the other methods, depending on the definition of the ROIs and the characteristics of the analysis software. This suggests that a combined approach using SPECT/CT and planar images is preferable for dosimetry.

In positron emission tomography/computed tomography (PET/CT), CT is typically used for attenuation correction during the creation and reconstruction of PET images. Respiratory motion can cause artifacts due to misalignment of PET images, known as respiratory misalignment artifacts (RMA), which occur in up to 30

OBJECTIVE:Lymphatic scintigraphy using radioisotope agents is a good method for evaluating the lymph flow status of patients with lower-limb lymphedema. To depict wide regions of lower-limb lymphatic vessels, at our institution, we administer radioisotopes at four locations in each limb when lymphatic scintigraphy images are to be obtained. Herein, we evaluated the correlation of lymphatic scintigraphy with lymphedema staging and investigated the usefulness of this four-point dermal-injection lymphatic scintigraphy (LyS4). MATERIALS AND METHODS:The 52 lower limbs of 26 patients (23 females, three males, aged 20-85 years, median 65 years) underwent a LyS4 examination of their lower limbs. The stage of lower-limb lymphedema was diagnosed by plastic surgeons at our institution using the International Society of Lymphology (ISL) staging system. The patients' ISL stages were stage 0 (n=20), stage 1 (n=7), and stage 2 (n=25). No patient was stage 3. For each LyS4 examination, technetium-99m human serum albumin diethylenetriamine pentaacetic acid (99mTc-HSA) was injected. The four injection points were the first interdigital web, slightly below the area of the lateral malleolus, slightly below the area of the medial malleolus, and the lateral side of the feet near the fifth digit of both feet. Using the planar LyS4 images, we investigated the positive/negative appearance of the four lymphatic vessel regions, i.e., anteromedial (AM), anterolateral (AL), posteromedial (PM), and posterolateral (PL) and the dermal backflow (DB). We then examined the correlations of these parameters with the ISL stage. RESULTS:The absence of AM, the absence of PM, the appearance of DB, and the number of lymphatic vessels depicted were each significant factors for distinguishing lymphedema. The appearance of DB and the number of lymphatic vessels depicted can distinguish moderate lymphedema (ISL stage 0 or 1) from severe lymphedema (ISL stage 2e or 2d). Regarding the diagnostic performance of the LyS4 parameters, high accuracy was observed for the appearance of PM (0.71), that of DB (0.79), and the number of depicted lymphatic vessels (0.77). CONCLUSION:LyS4 is a useful method with good correlation with the ISL stage in patients with lower-limb lymphedema.

Objective L-methyl-11C-methionine (MET)- and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) are used to detect gliomas. However, the efficacy of MET-PET and FDG-PET in detecting gene alterations in gliomas remains unclear. Therefore, in this study, we evaluated the relationship between genetic alterations and PET tracer uptake in diffuse astrocytic glioma. Methods Thirty-two patients who had been newly diagnosed with astrocytic gliomas at Kagoshima University and Kyushu University and had undergone MET-PET and FDG-PET were enrolled. They underwent analysis of glioma-related gene expression using a customized 48-gene panel. Results The tumors identified in this study were classified as follows: glioblastomas, isocitrate dehydrogenase (IDH) wildtype (n = 15); astrocytic glioma, IDH-mutant, World Health Organization (WHO) grade 4 (n = 2); astrocytic glioma, IDH-mutant, WHO grade 3 (n = 4); astrocytic glioma, IDH-mutant, WHO grade 2 (n = 7); and diffuse astrocytic glioma, not elsewhere classified (n = 4). Astrocytic tumors with IDH mutations, ATRX mutations, and/or loss of function (mut/loss) had a significantly lower tumor-to-normal tissue (T/N) ratio on the MET-PET and FDG-PET images compared with those without these alterations. Astrocytic tumors with CDKN2A/B homozygous deletions (HD), EGFR mutation and/or amplification (mut/amp), or PTEN mut/loss had a significantly higher T/N ratio on the MET-PET images compared with those without these alterations. Astrocytic tumors with NF1 mut/loss had a significantly higher T/N ratio on their FDG-PET images compared with those without these alterations. The cut-off T/N ratio for the MET-PET images for the identification of EGFR mut/amp was 4.50 (sensitivity: 95%; specificity: 56%, AUC: 0.77), and that for detecting CDKN2A/B HDwas 2.32 (sensitivity: 72%; specificity: 86%; AUC: 0.85). Conclusion These findings from our small, retrospective cohort study suggest that MET-PET and FDG-PET are potentially valuable approaches for preoperatively predicting the molecular status of gliomas, particularly for assessing tumors with EGFR mut/amp and CDKN2A/B HD. Preoperative genetic alteration prediction in astrocytic gliomas based on PET tracer uptake may provide accurate information for patients and inform clinical decision-making. Multicenter prospective trials are essential.

To evaluate whether the combination of amide proton transfer-weighted imaging (APT-WI) and methionine positron emission tomography (MET-PET) enhances the non-invasive prediction of isocitrate dehydrogenase (IDH) mutation status in adult diffuse gliomas. We retrospectively analysed 28 adult patients with histologically confirmed diffuse gliomas who underwent preoperative APT-WI and MET-PET imaging at our institution. Histogram analyses were conducted for both imaging modalities, extracting parameters such as the 10th, 50th, 70th, and 90th percentiles, mean, variance, skewness, and kurtosis. Parameters between IDH-mutant and IDH-wildtype gliomas were compared using the Mann–Whitney U test. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, and combined models of the two parameters were constructed using multivariable logistic regression. IDH-wildtype gliomas exhibited significantly higher APT-WI 90th percentile (APT90) values (median: 3.51

Diagnostic reference levels (DRLs) are practical benchmarks for optimizing patient radiation exposure in medical imaging. In Japan, national DRLs, including those for nuclear medicine together and other radiological procedures, were first established in 2015 and revised in 2020. In this study, we revised the DRL values of nuclear medicine for the establishment of DRLs2025, based on data collected from institutions nationwide throughout Japan. Data were collected via an online survey from facilities performing nuclear medicine procedures, including SPECT, PET, and hybrid CT imaging. Information on dose activity of the administered radiopharmaceuticals and CT parameters (CTDIvol and DLP) were collected. DRL values were determined through analysis of the submitted data, supplemented by panel discussions among experts taking into account the clinical appropriateness of the values and various technological factors. Overall, the newly established DRLs2025 demonstrated a decreasing trend in administered radiopharmaceutical activities, CTDIvol, and DLP compared with the previous surveys. This trend reflects ongoing efforts toward the optimization of radiation exposure and radiopharmaceutical dose reduction, likely driven by the introduction of image reconstruction methods based on newer technologies. However, substantial interfacility variations were observed, particularly in the CT parameters, suggesting disparities in equipment, imaging protocols, and the balance between image quality and radiation dose. The establishment of DRLs2025 underscores continued progress in optimizing radiation exposure in nuclear medicine practice in Japan. Although issues regarding data variability and quality remain, DRLs continue to be a key tool in radiation protection and quality assurance. Ongoing efforts to improve data collection systems and to align procedures with international standards are essential for the future refinement of DRLs.

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

Introduction: Sarcoidosis is a systemic granulomatous disease of unknown cause, and cardiac involvement impacts its prognosis. Isolated cardiac sarcoidosis (iCS) has increasingly been recognized; however, its prognosis and efficacy of immunosuppressive therapy remains undetermined. The aim of this study is to clarify the clinical features and outcomes of patients with iCS and systemic sarcoidosis including cardiac involvement (sCS) receiving immunosuppressive therapy. Methods and Results: We retrospectively reviewed the clinical data of 42 patients with sCS and 30 with iCS diagnosed at our institution between 2004 and 2022. We compared the characteristics, and the rate of adverse cardiac events including cardiac death, fatal ventricular tachyarrhythmia, and heart failure hospitalization between groups. The median follow-up duration was 1535 [630, 2555] days, without significant difference between groups. There were no significant differences in sex, NYHA class, and left ventricular ejection fraction between groups. Immunosuppressive agents were administered in 86% of sCS and in 73% of iCS. When analyzed only with patients receiving immunosuppressive therapy (sCS, n=36; iCS, n=21), the cardiac event-free survival was significantly lower in iCS patients than sCS patients (37% vs. 79%, p=0.002). Multivariate analysis showed that iCS was an independent determinant for predicting adverse cardiac events. We evaluated the disease activity in 26 sCS and 16 iCS patients by quantitative measures of FDG-PET including cardiac metabolic volume and total lesion glycolysis, representing accurate three-dimensional distribution and intensity of inflammation. Although iCS patients had lower baseline disease activity than sCS patients, immunosuppressive therapy did not attenuate disease activity in iCS patients in contrast to sCS. Conclusions: iCS showed poorer response to immunosuppressive therapy and worse cardiac prognosis than sCS.

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non- 18 F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

Background/Aim: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. Patients and Methods: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. Results: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. Conclusion: 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.

211At is a promising nuclide for targeted radioisotope therapy. Direct imaging of this nuclide is important for in vivo evaluation of its distribution. We investigated suitable conditions for single-photon emission computed tomography (SPECT) imaging of 211At and assessed their feasibility using a homemade Monte Carlo simulation code, MCEP-SPECT. Radioactivity concentrations of 5, 10, or 20 kBq/mL were distributed in six spheres in a National Electrical Manufactures Association (NEMA) body phantom with a background of 1 kBq/mL. The energy window, projection number, and acquisition time were 71–88 keV, 60, and 60 s, respectively, per projection. A medium-energy collimator and three low-energy collimators were tested. SPECT images were reconstructed using the ordered subset expectation maximization (OSEM) method with attenuation correction (Chang method) and scatter correction (triple-energy-windows method). Image quality was evaluated using the contrast-to-noise ratio (CNR) for detectability and the contrast recovery coefficient (CRC) for quantitavity. The low-energy, high-sensitivity collimator exhibited the best detectability among the four types of collimators, with a maximum CNR value of 43. In contrast, the low-energy, high-resolution collimator exhibited excellent quantitavity, with a maximum CRC value of 102

To evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. Among 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. Nineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. Post-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.

Recently, positron emission tomography (PET) with fibroblast activation protein inhibitor (FAPI) has gained significant attention as an advanced tumor diagnostic imaging tool. FAPI PET has a promising potential owing to its ability to accurately depict most malignant tumors. It has an accuracy that is comparable to or surpassing the diagnostic accuracy of PET using 18F-fluorodeoxyglucose (FDG). Moreover, FAPI PET can identify malignant lesions that may be inconclusive on FDG PET. Beyond its application in neoplastic disorders, there have been encouraging reports suggesting the utility of FAPI PET in non-neoplastic conditions such as respiratory or cardiac diseases. This article aimed to provide a comprehensive overview of the recently published articles investigating FAPI and discuss its clinical utility with an emphasis on its application in tumor diagnostics. Numerous radiopharmaceutical FAPIs, including 18F- and 68Ga-labeled compounds, have been developed, and they offer various advantages and applications. With the progress in the FAPI PET synthesis to enhance accumulation and retention in pathological lesions, future studies are expected to provide valuable data on its therapeutic efficacy.