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Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to Aβ plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing Aβ plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Aβ and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Aβ. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM♂/WM♀ > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to Aβ plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new Aβ plaque PET imaging agent that exhibited high binding to Aβ plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of 18F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.

PurposeHigh blood glucose (hBG) in patients undergoing [18F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations.Materials and methodsOncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose ( 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria.ResultsThirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUVmean, 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUVmax, 7.58 ± 0.74 vs. 13.38 ± 3.94; p  11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08).ConclusionWhile elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible.

PURPOSE: Long axial field-of-view (LAFOV) positron emission tomography (PET) systems allow to image all major organs with one bed position, which is particularly useful for acquiring whole-body dynamic data using short-lived radioisotopes like 82Rb. METHODS: We determined the absorbed dose in target organs of three subjects (29, 40, and 57 years old) using two different methods, i.e., MIRD and voxel dosimetry. The subjects were injected with 407.0 to 419.61 MBq of [82Rb]Cl and were scanned dynamically for 7 min with a LAFOV PET/CT scanner. RESULTS: Using the MIRD formalism and voxel dosimetry, the absorbed dose ranged from 1.84 to 2.78 μGy/MBq (1.57 to 3.92 μGy/MBq for voxel dosimetry) for the heart wall, 2.76 to 5.73 μGy/MBq (3.22 to 5.37 μGy/MBq for voxel dosimetry) for the kidneys, and 0.94 to 1.88 μGy/MBq (0.98 to 1.92 μGy/MBq for voxel dosimetry) for the lungs. The total body effective dose lied between 0.50 and 0.76 μSv/MBq. CONCLUSION: Our study suggests that the radiation dose associated with [82Rb]Cl PET/CT can be assessed by means of dynamic LAFOV PET and that it is lower compared to literature values.

BACKGROUND: Double lumen endobronchial tubes (DLTs) are frequently used to employ single lung ventilation strategies during thoracic surgical procedures. Placement of these tubes can be challenging even for experienced clinicians. We hypothesized that airway anatomy, particularly of the glottis and proximal trachea, significantly impacts the ease or difficulty in placement of these tubes. METHODS: Images from 24 randomly selected Positron Emission Tomography - Computed Tomography (PET-CT) scans were evaluated for several anatomic aspects of the upper airway, including size and angulation of the glottis and proximal tracheal using calibrated CT measurements and an online digital protractor. The anatomic issues identified were confirmed in cadaveric anatomic models. RESULTS: Proximal tracheal diameter measurements in PET-CT scans demonstrated a mean ± standard deviation of 20.4 ± 2.5 mm in 12 males and 15.5 ± 0.98 mm in 12 females (p

Quantitative PET attenuation correction (AC) for cardiac PET/CT and PET/MR is a challenging problem. We propose and evaluate an AC approach that uses coincidences from a relatively weak and physically fixed sparse external source, in combination with that from the patient, to reconstruct μ -maps based on physics principles alone. The low 30 cm3 volume of the source makes it easy to fill and place, and the method does not use prior image data or attenuation map assumptions. Our supplemental transmission aided maximum likelihood reconstruction of attenuation and activity (sTX-MLAA) algorithm contains an attenuation map update that maximizes the likelihood of terms representing coincidences originating from tracer in the patient and a weighted expression of counts segmented from the external source alone. Both external source and patient scatter and randoms are fully corrected. We evaluated performance of sTX-MLAA compared to reference standard CT-based AC with FDG PET/CT phantom studies; including modeling a patient with myocardial inflammation. Through an ROI analysis we measured ≤ 5 % bias in activity concentrations for PET images generated with sTX-MLAA and a TX source strength ≥ 12.7 MBq, relative to CT-AC. PET background variability (from noise and sparse sampling) was substantially reduced with sTX-MLAA compared to using counts segmented from the transmission source alone for AC. Results suggest that sTX-MLAA will enable quantitative PET during cardiac PET/CT and PET/MR of human patients.

PurposeMultiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [89Zr]Zr-DFO-YS5 for imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [89Zr]Zr-DFO-YS5 for immunoPET imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models.Experimental designIn vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [89Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [225Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity.Results[89Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (Kd = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [89Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [225Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups.ConclusionsOur study showed that the CD46-targeted probe [89Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [225Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.

PurposeThis study examines clinical, functional, and CT metrics of sarcopenia and all-cause mortality in older adults undergoing outpatient imaging.MethodsThe study included outpatients ≥ 65 years of age undergoing CT or PET/CT at a tertiary care institution. Assessments included screening questionnaires for sarcopenia (SARC-F) and frailty (FRAIL scale), and measurements of grip strength and usual gait speed (6 m course). Skeletal muscle area (SMA), index (SMI, area/height2) and density (SMD) were measured on CT at T12 and L3. A modified SMI was also examined (SMI-m, area/height). Mortality risk was studied with Cox proportional hazard analysis.ResultsThe study included 416 patients; mean age 73.8 years [sd 6.2]; mean follow-up 2.9 years (sd 1.34). Abnormal grip, SARC-F, and FRAIL scale assessments were associated with higher mortality risk (HR [95%CI] = 2.0 [1.4-2.9], 1.6 [1.1-2.3], 2.0 [1.4-2.8]). Adjusting for age, higher L3-SMA, T12-SMA, T12-SMI and T12-SMI-m were associated with lower mortality risk (HR [95%CI] = 0.80 [0.65-0.90], 0.76 [0.64-0.90], 0.84 [0.70-1.00], and 0.80 [0.67-0.90], respectively). T12-SMD and L3-SMD were not predictive of mortality. After adjusting for abnormal grip strength and FRAIL scale assessments, T12-SMA and T12-SMI-m remained predictive of mortality risk (HR [95%CI] = 0.83 [0.70-1.00] and 0.80 [0.67-0.97], respectively).ConclusionCT areal metrics were weaker predictors of all-cause mortality than clinical and functional metrics of sarcopenia in our older patient cohort; a CT density metric (SMD) was not predictive. Of areal CT metrics, SMI (area/height2) appeared to be less effective than non-normalized SMA or SMA normalized by height1.

Opinion statementPSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.

ObjectivesWe characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification.MethodsIn this retrospective study, CUP cases were categorized as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short-term posttreatment (3-6 months after completion of treatment) weights, PHQ-9, Eating Assessment Tool (EAT-10), and Voice Handicap Index (VHI-10) scores were compared between UP and KP.ResultsAmong 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV-positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ-9, EAT-10, and VHI-10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (-14.1% vs. -7.6%, p = 0.032), higher EAT-10 scores (12.5 vs. 3, p = 0.004), and higher PHQ-9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating.ConclusionKP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes.Level of evidence4 Laryngoscope, 134:701-707, 2024.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

BackgroundHypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.ResultsThirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV.Conclusions[18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

PurposeInflamed, prone-to-rupture coronary plaques are an important cause of myocardial infarction and their early identification is crucial. Atherosclerotic plaques are characterized by overexpression of the type-2 somatostatin receptor (SST2) in activated macrophages. SST2 ligand imaging (e.g. with [68 Ga]Ga-DOTA-TOC) has shown promise in detecting and quantifying the inflammatory activity within atherosclerotic plaques. However, the sensitivity of standard axial field of view (SAFOV) PET scanners may be suboptimal for imaging coronary arteries. Long-axial field of view (LAFOV) PET/CT scanners may help overcome this limitation. We aim to assess the ability of [68 Ga]Ga-DOTA-TOC LAFOV-PET/CT in detecting calcified, SST2 overexpressing coronary artery plaques.MethodsIn this retrospective study, 108 oncological patients underwent [68 Ga]Ga-DOTA-TOC PET/CT on a LAFOV system. [68 Ga]Ga-DOTA-TOC uptake and calcifications in the coronary arteries were evaluated visually and semi-quantitatively. Data on patients' cardiac risk factors and coronary artery calcium score were also collected. Patients were followed up for 21.5 ± 3.4 months.ResultsA total of 66 patients (61.1%) presented with calcified coronary artery plaques. Of these, 32 patients had increased [68 Ga]Ga-DOTA-TOC uptake in at least one coronary vessel (TBR: 1.65 ± 0.53). Patients with single-vessel calcifications showed statistically significantly lower uptake (SUVmax 1.10 ± 0.28) compared to patients with two- (SUVmax 1.31 ± 0.29, p

Misregistration between CT and PET in PET/CT is mainly caused by respiratory motion or irregular respiration during the CT scan in PET/CT. Other than repeat CT, repeat PET/CT, or data-driven gated (DDG) CT, there is no practical approach to mitigate the misregistration artifacts and subsequent CT attenuation correction (CTAC) of the PET data. DDG PET derives a respiratory motion model based on the multiple phases of PET images without hardware gating and it allows for a potential correction of the misregistration artifacts based on the respiratory motion model. The purpose of this commentary was to compare the recent two publications on matching the random phase of helical CT with one of the PET phases derived from the motion model of DDG PET and warping the misregistered helical CT for CTAC of and registration with PET or DDG PET. The two publications were similar in methodology. However, the data sets used for the comparison were different and could potentially impact their conclusions. [ABSTRACT FROM AUTHOR]

Background: Extraskeletal mesenchymal chondrosarcoma (ESMC), an uncommon and highly aggressive form of chondrosarcoma, is characterized by its mesenchymal origin and absence of skeletal involvement. Only a few cases of primary ESMC with metastasis to the pancreas have been reported so far. In this study, we present a case of ESMC in the left thigh with a solitary pancreatic metastasis in a 45-year-old woman. Additionally, we provide a thorough overview of ESMC, encompassing its entire clinical progression and radiographic observations. Furthermore, we reviewed all thirteen cases of pancreatic metastasis, including this present case, analyzing patient attributes, clinical management, and prognosis. Case presentation: A 45-year-old woman has had a painless mass in her left thigh for one year. X-ray, computed tomography (CT), andmagnetic resonance imaging of the left thigh were performed. Positron emission tomography-CT imaging showed a high accumulation in the left thigh tumor and the pancreatic neck lesion. A diagnosis of extraskeletal chondrosarcoma with pancreatic metastasis was determined based on the radiological examinations. A final diagnosis of ESMC was confirmed by histopathological and immunohistochemical examinations after surgical resection. The patient presentedmetastasis in the lung, right groin, and tail of the pancreas successively, and mostly received complete surgical excision during a 39-month follow-up with postoperative chemotherapy. Conclusion: We present a highly uncommon case of ESMC spreading to the pancreas and highlight the importance of recognizing the distinctive imaging features of ESMC for diagnosis and prognosis assessment. [ABSTRACT FROM AUTHOR]

Introduction: Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis. Methods: Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years. They were followed up for a maximum period of 18 months. Clinical data were summarized and prognostic factors including demographic characteristics, laboratory tests, and neurological functions were compared between survived and deceased patients at 18 months follow-up. Results: Twenty-six patients, 10 females (38.5%) and 16 males (61.5%), diagnosed with anti-GABABR encephalitis were studied. The median age was 58 years. Of the 23 cases with complete clinical data, their main manifestations were epileptic seizures (65%), mental and behavioral abnormalities (52%), and cognitive impairment (48%). 7 (30.4%) cases had tumors: 5 small cell lung cancer (SCLC), 1 rectum adenocarcinoma (moderately differentiated) and 1 esophageal squamous cell carcinoma. MRI showed 5 (22%) cases had T2 FLAIR increased signals in cortex but with different regions affected. One of the two patients scanned for PET-CT showed hypermetabolism in the left temporal lobe region. The disease course ranged from 5 days to 3 years. 2 patients (one had esophageal carcinoma) without immunotherapy and 3 patients (one had SCLC) that did not response to immunotherapy died soon after diagnosis. 18 patients improved after immunotherapy while 3 (all had SCLC) died after relapses. The prevalence of epileptic seizures and malignancies was significantly lower in the survival group than in the deceased group at 18-months follow-up, the same as the admission mRs score. Serum fibrinogen, cerebrospinal fluid immunoglobulin G quotient, and 24-hour intrathecal synthesis rate were significantly lower in the survival groups as well. Conclusions: Cortex T2 FLAIR abnormalities were only observed in a small proportion of anti-GABABR encephalitis patients with heterogeneous MRI phenotypes. High mRS score at admission, epileptic seizures and the presence of a tumor indicated a poor prognosis, while the underlying mechanism of the later two factors should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. 18F-fluoride uptake in newly formed bone can be evaluated using [18F]NaF (i.e., sodiumfluoride) PET/CT, identifying active areas of bone formation in FOP. The purpose of this study was to assess the performance of various semi-quantitative methods with full kinetic analysis. Results: Seven patients (age range: 20-31 years) with FOP underwent dynamic [18F] NaF scans at baseline and after one year. [18F]NaF uptake was measured in aorta descendens, vertebrae, heterotopic bone lesions and metabolically active regions on PET, and quantified using nonlinear regression (NLR) analysis together with standardized uptake value (SUV) and target-to-blood ratio (TBR). SUV was on measured the 40-45 min frame of the dynamic sequence (SUV40-45) and on the subsequent static sweep (SUVStatic). Correlations between and SUV40-45 and NLR-derived Ki were comparable when normalized to body weight (r=0.81, 95% CI 0.64-0.90), lean body mass (r = 0.79, 95% CI 0.61-0.89) and body surface area (r = 0.84, 95% CI 0.70-0.92). Correlation between TBR40-45 and NLR-derived Ki (r=0.92, 95% CI 0.85-0.96) was higher than for SUV40-45. Correlation between TBR40-45 and NLR-derived Ki was similar at baseline and after one year (r=0.93 and 0.94). The change in TBR40-45 between baseline measurement and after one year correlated best with the change in NLR-derived Ki in the PET-active lesions (r=0.87). Conclusion: The present data supports the use of TBR for assessing fluoride uptake in PET-active lesions in FOP. Clinical trial registration: Sub-study of the Lumina-1 trial (clinicaltrials.gov, NCT03188666, registered 13-06-2017). [ABSTRACT FROM AUTHOR]

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a 36-year-old male with drug-resistant post-traumatic epilepsy who achieved seizure freedom without medication after stereoelectroencephalography (sEEG) implantation. The patient underwent sEEG monitoring, which captured a single event without sEEG correlate, prompting further investigation. Despite discontinuing all seizure medications, the patient remained seizure-free for over 3.5 years. The article highlights the potential benefits and risks of sEEG procedures in drug-resistant epilepsy cases, emphasizing the need for further research into potential tissue injury caused by depth electrode insertion. [Extracted from the article]

Background: As the spatial resolution of positron emission tomography (PET) scanners improves, understanding of radiotracer distributions in tissues at high resolutions is important. Hence, we propose a method for co-registration of high-resolution ex vivo specimen PET images, combined with computed tomography (CT) images, and the corresponding specimen histopathology. Methods: We applied our co-registration method to breast cancer (BCa) specimens of patients who were preoperatively injected with 0.8 MBq/kg [ 18 F]fluorodeoxyglucose ([18F]FDG). The method has two components. First, we used an image acquisition scheme that minimises and tracks tissue deformation: (1) We acquired sub-millimetre (micro)-PET-CT images of ±2 mm-thick lamellas of the fresh specimens, enclosed in tissue cassettes. (2) We acquired micro-CT images of the same lamellas after formalin fixation to visualise tissue deformation. (3) We obtained 1 hematoxylin and eosin (H&E) stained histopathology section per lamella of which we captured a digital whole slide image (WSI). Second, we developed an automatic co-registration algorithm to improve the alignment between the micro-PET-CT images and WSIs, guided by the micro-CT of the fixated lamellas. To estimate the spatial co-registration error, we calculated the distance between corresponding microcalcifications in the micro-CTs and WSIs. The co-registered images allowed to study standardised uptake values (SUVs) of different breast tissues, as identified on the WSIs by a pathologist. Results: We imaged 22 BCa specimens, 13 cases of invasive carcinoma of no special type (NST), 6 of invasive lobular carcinoma (ILC), and 3 of ductal carcinoma in situ (DCIS). While the cassette framework minimised tissue deformation, the best alignment between the micro-PET-CT images and WSIs was achieved after deformable co-registration. We found an overall average co-registration error of 0.74 ± 0.17 mm between the micro-PET images and WSIs. (Pre)malignant tissue (including NST, ILC, and DCIS) generally showed higher SUVs than healthy tissue (including healthy glandular, connective, and adipose tissue). As expected, inflamed tissue and skin also showed high uptake. Conclusions: We developed a method to co-register micro-PET-CT images of surgical specimens and WSIs with an accuracy comparable to the spatial resolution of the micro-PET images. While currently, we only applied this method to BCa specimens, we believe this method is applicable to a wide range of specimens and radiotracers, providing insight into distributions of (new) radiotracers in human malignancies at a sub-millimetre resolution. [ABSTRACT FROM AUTHOR]

Rare cases of arsenical keratosis are attributed to the ingestion of arseniccontaining traditional Chinese medicines for conditions such as psoriasis. Arsenic is a potent carcinogen, and squamous cell carcinoma is known to develop in arsenical keratosis. A 51-year-old male patient with a 30-year history of psoriasis and a history of arsenic poisoning presented with suppuration, ulceration, and pain one and a half years after trauma to the right thumb. These symptoms had recurred after wound debridement, lesion resection, and pedicle flap transplantation. Histopathological examination of the skin lesions had suggested squamous cell carcinoma, and subsequent PET-CT examination had shown proliferation and enlargement of lymph nodes. Following right forearm amputation and radiofrequency ablation, additional lumps had been observed, but the patient had declined further surgery. Physical examination showed palpable enlarged axillary lymph nodes, which was confirmed by ultrasound. After three cycles of first-line immunotherapy with toripalimab combined with albumin paclitaxel and cisplatin chemotherapy, masses in the right upper arm were reduced. This case highlights the risks of arsenic-containing medicines used for treating psoriasis. Attention should be paid to the use of standardized treatments in psoriasis, as well as the probability of malignant transformation in arsenical keratosis. [ABSTRACT FROM AUTHOR]

Background: Intramuscular hemangioma is a vascular malformation occurring in muscle tissues. It is most common in skeletal muscles of limbs, especially lower limbs in childhood. The intercostal intramuscular hemangioma with sternal invasion is very rare. Case presentation: The 47-year-old female patient was hospitalized due to "suddenly chest pain for 4 days". Chest contrast-enhanced CT indicated bony changes in the sternum, accompanied by soft tissue shadows in the posterior sternum and diaphragmatic angle. After admission, physical examination showed: peristernal tenderness, percussion pain, other no obvious positive signs. PET-CT examination indicated that there was a high possibility of benign sternal changes. No cancer cells were found by sternal puncture. Surgical biopsy was performed and pathological findings were consistent with intramuscular hemangioma. Conclusion: Intramuscular hemangioma with bone invasion is very rare, imaging examination is difficult to indicate obvious evidence, preoperative diagnosis is difficult, complete surgical resection is very important, more personalized treatment should be provided according to the overall situation of the patient. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the findings of a study on a patient with NFkB1 haploinsufficiency, a condition associated with lymphadenopathy and an increased risk of lymphoma. The study found that the patient had impaired cell death pathways in response to certain stimuli, indicating a dysfunction in apoptosis. The authors suggest that dysregulated apoptosis may contribute to the development of lymphoproliferative disorders in patients with NFkB1 haploinsufficiency and propose further research to explore potential therapeutic targets. The patient in the study has opted for close monitoring rather than treatment. [Extracted from the article]

Introduction: In this study, we investigated the clinical outcomes of patients who underwent surgery with proven lymph node metastasis. Methods: Patients who were operated for lung cancer with pN1 or pN2 were examined in the study. The clinicopathological features and survival of the subjects were evaluated according to pN1‐pN2 status, presence of neoadjuvant treatment, Positron emission tomography and computed tomography (PET/CT) avidity on mediastinal lymph nodes and specific lymph node stations. Results: The study examines 100 patients operated from January 2016 to December 2021. Number of cases with pN1 and pN2 disease were 45 (45%) and 55 (55%) respectively. Thirty (30%) patients received neoadjuvant treatment. The 5‐year overall survival (OS) and disease‐free survival (DFS) of the patients were computed as 42.5% and 42.4% correspondingly. The 5‐year cancer‐related survival was 55.3%. In pN2 cohort, 5‐year DFS was 67.9% in the neoadjuvant group and 15.9% in the non‐neoadjuvant group (P = 0.042). In non‐neoadjuvant group, 5‐year DFS was 19.9% in cases with mediastinal PET/CT avidity and 56.3% in patients without mediastinal PET/CT avidity (P = 0.018). In pN2 disease, the presence of subcarinal or paratracheal lymph node metastasis did not create a significant difference in 5‐year OS or DFS, but pulmonary ligament lymph node metastasis was found to be linked with worse survival in both 5‐year OS (P = 0.005) and DFS (P = 0.017). Conclusion: The main elements related with poor prognosis were absence of neoadjuvant treatment and pulmonary ligament lymph node metastasis in pN2 disease, detecting PET/CT avid mediastinal lymph nodes in non‐neoadjuvant group. [ABSTRACT FROM AUTHOR]

The article from the Journal of Medical Imaging & Radiation Oncology discusses the use of low-dose VMAT radiotherapy for treating actinic keratosis, a condition that can affect large areas of the skin. The study conducted at Sir Charles Gairdner Hospital in Perth, Australia, analyzed patients treated for actinic keratosis and found that VMAT radiotherapy resulted in a complete response in 100% of treated areas, with favorable patient-reported outcomes. The study demonstrated excellent short-term response with lower doses than previously published data, highlighting the potential of this treatment for actinic keratosis. [Extracted from the article]

The article explores the impact of Clinical Decision Support (CDS) implementation on radiology workflow at a hospital in Melbourne, Australia, showing potential benefits such as reduced unnecessary test orders and improved resource utilization. Adherence to the STARD 2015 guideline in medical imaging DTA studies was found to be suboptimal, with recommendations for improving reporting to enhance research quality. Other studies evaluated the appropriateness of imaging requests in emergency departments, overuse of neuroimaging, and the association of certain signs with injury severity in motor vehicle collision patients. Additionally, AI models were successful in identifying missed cancers in breast screening programs, indicating their potential to enhance cancer detection. [Extracted from the article]

Objective: The aim of this study was to develop an F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomic model for predicting mediastinal lymph node metastasis (LNM) in presurgical patients with lung adenocarcinoma. Methods: The study enrolled 320 patients with lung adenocarcinoma (288 internal and 32 external cases) and extracted 190 radiomic features using the LIFEx package. Optimal radiomic features to build a radiomic model were selected using the least absolute shrinkage and selection operator algorithm. Logistic regression was used to build the clinical and complex (combined radiomic and clinical variables) models. Results: Ten radiomic features were selected. In the training group, the area under the receiver operating characteristic curve of the complex model was significantly higher than that of the radiomic and clinical models [0.924 (95% CI: 0.887-0.961) vs. 0.863 (95% CI: 0.814-0.912; p = 0.001) and 0.838 (95% CI: 0.783-0.894; p = 0.000), respectively]. The sensitivity, specificity, accuracy, and positive and negative predictive values of the radiomic model were 0.857, 0.790, 0.811, and 0.651 and 0.924, respectively, which were better than that of visual evaluation (0.539, 0.724, 0.667, and 0.472 and 0.775, respectively) and PET semiquantitative analyses (0.619, 0.732, 0.697, and 0.513 and 0.808, respectively). Conclusions:18F-FDG PET/CT radiomics showed good predictive performance for LNM and improved the N-stage accuracy of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The article in the Clinical & Experimental Dermatology journal presents a case report of a 60-year-old male patient with mycosis fungoides (MF) exhibiting palmar and axillary nodules with syringotropism. The patient had been misdiagnosed with adult-onset atopic dermatitis for over 10 years. Histopathological examinations revealed dense cellular infiltration without epidermotropism, and Elastica van Gieson staining showed a loss of elastic fibers. The patient was diagnosed with MF T3NxM0 stage IIB and treated with medication, radiation, and therapy, leading to remission of cutaneous manifestations. The case highlights the importance of recognizing rare subtypes of MF and the significance of deep cuts in confirming syringotropism in low-grade cutaneous T-cell lymphomas. [Extracted from the article]

A 25-year-old man presented with a rash, headache, confusion, and speech problems following an upper respiratory tract infection. He exhibited various neurological symptoms and cutaneous manifestations resembling erythema nodosum. After extensive testing, he was diagnosed with Neuro-Sweet syndrome, a rare condition characterized by febrile neutrophilic dermatosis and neurological manifestations. Treatment with systemic corticosteroids led to significant improvement in his symptoms, highlighting the importance of early diagnosis and appropriate management in such cases. [Extracted from the article]

Background Patients with melanoma present a high risk of developing extracutaneous metastases. Positron emission tomography–-computed tomography (PET-CT) is one of the preferred examinations for the staging of oncological patients. It is not the method of choice to detect brain metastases, but this technique has shown significant improvement and allows the detection of some of them. However, it is unclear how it performs compared with magnetic resonance imaging (MRI), the current gold standard for diagnosing brain metastases. Objectives To compare the accuracy of PET-CT and cerebral MRI to detect brain metastases in patients with melanoma. Methods We retrospectively included all patients diagnosed with melanoma stage IIC–IV (American Joint Committee on Cancer 8th Edition, 2017) who presented at the skin tumour board of the University Hospital of Bern between January 2018 and December 2022. All radiological reports extracted from the patient management system were analysed to assess discrepancy between the visibility of brain metastases on PET-CT and brain MRI. Results In this study including 393 patients, brain MRI demonstrated significantly better performance than PET-CT in detecting brain metastases. In 47 patients, cerebral metastases were detected completely, detected partially, or not detected by PET-CT in 2 (4%), 15 (32%) and 30 (64%), respectively. Conclusions Despite the increasing performance of PET-CT, this study highlights the crucial role of brain MRI, which remains the gold standard to detect cerebral metastases. Brain MRI should be performed in patients with high-risk melanoma from stage IIC to exclude brain metastases. [ABSTRACT FROM AUTHOR]

Background: Linear attenuation coefficients (LACs) in positron emission tomography combined with computed tomography (PET/CT) are derived from CT scans that utilize energy‐integrating detectors (EID‐CT). These LACs are inaccurate when iodine contrast has been injected. Photon counting detector CT (PCD‐CT) may be able to improve the accuracy. Purpose: To investigate whether PCD‐CT can improve PET/CT quantitative accuracy. Methods: Two experiments were performed: one with CT only and one that combined PET and CT. The first experiment used an electron density phantom whose inserts were imaged with EID‐CT and PCD‐CT. The inserts simulated normal human tissues, including bone and iodinated blood. In the case of PCD‐CT, virtual‐monoenergetic images at 190 keV were created. LACs were derived in each case and compared against known values. For inserts with iodine, more accurate LACs were expected with PCD‐CT. The second experiment involved a custom PET phantom with various materials simulating human tissues (blood, iodinated blood, and bone) and 18F radioactivity. Data were first acquired with an EID‐CT‐based PET/CT system and then separately in a PCD‐CT system without PET. PET images were reconstructed using LAC from EID‐CT and PCD‐CT. PET image values were compared against known activity values using recovery coefficients (RC). Results: In the first experiment, LAC based on EID‐CT were in error by as much as 18%, whereas the corresponding PCD‐CT based measurements were within 3%. In the second experiment, minimum, maximum, and mean RC were (96.1%, 115.4%, and 103.8%) for the EID‐CT method, and (95.8%, 105.5%, and 101.0%) for the PCD‐CT method. The consistency of PET images in body and head orientations was improved. Conclusions: PCD‐CT can acquire the information needed for accurate LAC for PET reconstruction in a single spiral acquisition. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-iodine avid differentiated thyroid cancer (DTC) may be a diagnostic problem, especially in patients with an indeterminate response to treatment (i.e., with thyroglobulin (Tg) concentration in the range of 1–10 ng/mL). PET/CT with [18F]FDG may be a useful technique for visualizing non-iodine avid DTC lesions. Presented study assessed the usefulness of using exogenous stimulation with recombinant human TSH (rhTSH) before PET/CT with [18F]FDG in detecting non-iodine avid foci of DTC in patients with elevated sTg and negative 131I WBS and the usefulness of Tg concentration in predicting a positive result of [18F]FDG PET/CT in this type of patients and to determine the optimal Tg cut-off point for obtaining a positive [18F]FDG PET/CT result. In a retrospective analysis including 73 patients with DTC suspected of having non-iodine avid recurrence or metastases there was no effect of rhTSH stimulation on the sensitivity and specificity of PET/CT, but a positive impact on the number of lesions visible in the examination was observed. Moreover, rhTSH stimulation allowed for visualization of non-iodine avid lesions with lower Tg concentration. Introduction: Non-iodine avid metastases of differentiated thyroid cancer (DTC) can be found using PET/CT with a fluorine-18-labeled glucose analog ([18F]FDG). There are ongoing discussions on the appropriateness of using exogenous thyrotropin (TSH) stimulation before this examination. Material and Methods: In a retrospective study, 73 PET/CT scans with [18F]FDG performed after exogenous stimulation with recombinant human TSH (rhTSH) and without such stimulation were analyzed. All analyzed patients were suspected of having non-iodine-avid foci of DTC. Results: The stimulation with rhTSH before the PET/CT did not affect the percentage of positive results: 37.5% (18/48) with rhTSH and 40% (10/25) without rhTSH (p = 0.83). The analysis of the ROC curves established the cut-off thyroglobulin point for a positive PET/CT result separately for both subgroups. There was no statistically significant difference between obtaining a positive PET/CT result and the baseline thyroglobulin concentration (both stimulated and unstimulated). The exogenous stimulation of TSH prior to the PET/CT had no effect on the [18F]FDG uptake in the PET/CT lesions. Conclusions: PET/CT with [18F]FDG remains a useful method for the diagnosis of non-iodine-avid DTC lesions; in the presented group, a positive effect of rhTSH stimulation on the number of DTC foci visible in the PET/CT was found, but without affecting its effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia is a serious complication that can arise in patients with head and neck cancer due to both the disease and its treatments. It causes severe weight loss, muscle and fat depletion, and systemic inflammation, which significantly diminish patients' quality of life and survival. This study uses advanced machine learning techniques to improve the prediction and understanding of cachexia. By analyzing detailed imaging and clinical data, the research seeks to identify early signs of cachexia, providing insights that could help shape future management strategies. Our findings suggest that specific imaging biomarkers, particularly pancreatic volume, could play a crucial role in predicting cachexia, potentially leading to improved treatment outcomes for affected patients. Background/Objectives: Cancer-associated cachexia in head and neck squamous cell carcinoma (HNSCC) is challenging to diagnose due to its complex pathophysiology. This study aimed to identify metabolic biomarkers linked to cachexia and survival in HNSCC patients using [18F]FDG-PET/CT imaging and machine learning (ML) techniques. Methods: We retrospectively analyzed 253 HNSCC patients from Vienna General Hospital and the MD Anderson Cancer Center. Automated organ segmentation was employed to quantify metabolic and volumetric data from [18F]FDG-PET/CT scans across 29 tissues and organs. Patients were categorized into low weight loss (LoWL; grades 0–2) and high weight loss (HiWL; grades 3–4) groups, according to the weight loss grading system (WLGS). Machine learning models, combined with Cox regression, were used to identify survival predictors. Shapley additive explanation (SHAP) analysis was conducted to determine the significance of individual features. Results: The HiWL group exhibited increased glucose metabolism in skeletal muscle and adipose tissue (p = 0.01), while the LoWL group showed higher lung metabolism. The one-year survival rate was 84.1% in the LoWL group compared to 69.2% in the HiWL group (p < 0.01). Pancreatic volume emerged as a key biomarker associated with cachexia, with the ML model achieving an AUC of 0.79 (95% CI: 0.77–0.80) and an accuracy of 0.82 (95% CI: 0.81–0.83). Multivariate Cox regression confirmed pancreatic volume as an independent prognostic factor (HR: 0.66, 95% CI: 0.46–0.95; p < 0.05). Conclusions: The integration of metabolic and volumetric data provided a strong predictive model, highlighting pancreatic volume as a key imaging biomarker in the metabolic assessment of cachexia in HNSCC. This finding enhances our understanding and may improve prognostic evaluations and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to evaluate the role of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), in guiding the use of consolidative radiotherapy (RT) for DLBCL patients. The goal is to help avoid unnecessary RT for low-risk patients, as current guidelines are unclear, potentially leading to the overuse of RT. We analyzed the data of 349 patients and RT was associated with a significant improvement in time-to-progression amongst the DV4-5 patients but not the DV1-3 patients. Our data suggest that DLBCL patients with end-of-treatment PET-CT DV1-3 may not require consolidative RT. Background: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. Methods: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. Results: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0–42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13–0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40–1.81; p = 0.671) (interaction's p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10–0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40–1.86; p = 0.707) (interaction's p = 0.087). Conclusion: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The landscape of malignant peripheral nerve sheath tumours (MPNSTs) is usually challenging both in terms of recognition and management. Despite a low incidence in the general population (0.001%), MPNST is an important cause of mortality in the neurofibromatosis type 1 (NF1) population. It is essential for a multi-disciplinary collaboration to achieve the best possible outcome. The aim of our paper was to contribute with a comprehensive review from the literature of the best multi-modality ways that show improvements in terms of survival and address potential future treatment approaches based on the molecular alterations seen in these tumours. Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in the absence of an underlying genetic predisposition. The primary therapeutic approach is most often radical surgery, with non-surgical modalities playing an important role, especially in locally advanced or metastatic cases. The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Increased positron emission tomography (PET) scanner z-axis coverage provides an opportunity in pediatrics to reduce dose, anesthesia, or repeat scans due to motion. Objective: Recently, our digital PET scanner was upgraded from a 25-cm to a 30-cm z-axis coverage. We compare the two systems through National Electrical Manufacturing Association (NEMA) testing and evaluation of paired images from patients scanned on both systems. Materials and methods: NEMA testing and a retrospective review of pediatric patients who underwent clinically indicated 18F-fluorodeoxyglucose (FDG) PET computed tomography (PET/CT) on both systems with unchanged acquisition parameters were performed. Image quality was assessed with liver signal to noise ratio (SNR-liver) and contrast to noise ratio (CNR) in the thigh muscle and liver with results compared with an unpaired t-test. Three readers independently reviewed paired (25 cm and 30 cm) images from the same patient, blinded to scanner configuration. Results: Expansion to 30 cm increased system sensitivity to 29.8% (23.4 cps/kBq to 30.4 cps/kBq). Seventeen patients (6 male/11 female, median age 12.5 (IQR 8.3–15.0) years, median weight 53.7 (IQR 34.2–68.7) kg) were included. SNR-liver and CNR increased by 35.1% (IQR 19.0–48.4%) and 43.1% (IQR 6.2–50.2%) (P-value <0.001), respectively. All readers preferred images from the 30-cm configuration. A median of 1 (IQR 1–1) for fewer bed positions was required with the 30-cm configuration allowing a median of 91 (IQR 47–136) s for shorter scans. Conclusion: Increasing z-axis coverage from 25 to 30 cm on a current-generation digital PET scanner significantly improved PET system performance and patient image quality, and reduced scan duration. [ABSTRACT FROM AUTHOR]

Background: It has long been known that thyroid disease can lead to changes in energy metabolism, thermoregulation, and anxiety behavior. While these actions have been partially attributed to thyroid hormone (TH) receptor α1 (TRα1) action in the brain, the precise neuroanatomical substrates have remain elusive. Methods: We used PET-CT scans to identify brain regions affected by TH. We then inhibited TRα1 signaling specifically in the most affected region, the zona incerta (ZI), a still mysterious region previously implicated in thermogenesis and anxiety. To this end, we used an adeno-associated virus (AAV) expressing a dominant-negative TRα1R384C in wild-type mice and phenotyped the animals. Finally, we used tyrosine hydroxylase-Cre mice to test specifically the contribution of ZI dopaminergic neurons. Results: Our data showed that AAV-mediated inhibition of TRα1 signaling in the ZI lead to increased energy expenditure at thermoneutrality, while body temperature regulation remained unaffected. Moreover, circulating glucocorticoid levels were increased, and a mild habituation problem was observed in the open field test. No effects were observed when TRα1 signaling was selectively inhibited in dopaminergic neurons. Conclusions: Our findings suggest that altered TH signaling in the ZI is not involved in body temperature regulation but can affect basal metabolism and modulates stress responses. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study was to evaluate the cooccurrence of capsular liver lesions along with peritoneal carcinomatosis and hematogenous metastases in other regions of the body in ovarian cancer patients on follow-up F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/ computed tomography (PET/CT) studies. Methods: Consecutive 18F-FDG PET/CT studies of 54 women with ovarian cancer between August 2012 and January 2020 and a total of 192 scans were analysed retrospectively. All patients had at least one hepatic and/or capsular lesion with high 18F-FDG uptake and at least two PET/ CT examinations. Results: According to interpretation, of 54 patients with hepatic or capsular lesions, 44 (81.4%), 5 (9.3%) and 5 (9.3%) of them were concluded as perihepatic implants, hematogenous liver metastases and both, respectively. Accompanying peritoneal carcinomatosis on follow-up PET/CT images was found in 42 (95.4%) and 3 (60%) patients with solely capsular lesions and solely hematogenous liver metastases, respectively. Extrahepatic hematogenous organ metastases on follow-up PET/CT images were seen in 4 (9.0%) and 3 (60%) patients with solely capsular lesions and solely hematogenous liver metastases, respectively. Lungs, bones, spleen and brain were detected metastases sites. Conclusion: Cooccurrence of peritoneal carcinomatosis in other regions of abdomen was found to be higher in comparison to hematogenous organ metastases on consecutive PET/CT studies of ovarian cancer patients with capsular liver lesions. The primary opinion of the nuclear medicine physician is essential along with the other patient data for differential diagnosis and treatment approach in this particular patient group. [ABSTRACT FROM AUTHOR]

Introduction: Primary refractory disease affects 30–40% of patients diagnosed with DLBCL and is a significant challenge in disease management due to its poor prognosis. Predicting refractory status could greatly inform treatment strategies, enabling early intervention. Various options are now available based on patient and disease characteristics. Supervised machine-learning techniques, which can predict outcomes in a medical context, appear highly suitable for this purpose. Design: Retrospective monocentric cohort study. Patient population: Adult patients with a first diagnosis of DLBCL admitted to the hematology unit from 2017 to 2022. Aim: We evaluated in our Center five supervised machine-learning (ML) models as a tool for the prediction of primary refractory DLBCL. Main results: One hundred and thirty patients with Diffuse Large B-cell lymphoma (DLBCL) were included in this study between January 2017 and December 2022. The variables used for analysis included demographic characteristics, clinical condition, disease characteristics, first-line therapy and PET-CT scan realization after 2 cycles of treatment. We compared five supervised ML models: support vector machine (SVM), Random Forest Classifier (RFC), Logistic Regression (LR), Naïve Bayes (NB) Categorical classifier and eXtreme Gradient Boost (XGboost), to predict primary refractory disease. The performance of these models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, false positive rate, sensitivity, and F1-score to identify the best model. After a median follow-up of 19.5 months, the overall survival rate was 60% in the cohort. The Overall Survival at 3 years was 58.5% (95%CI, 51–68.5) and the 3-years Progression Free Survival was 63% (95%CI, 54–71) using Kaplan-Meier method. Of the 124 patients who received a first line treatment, primary refractory disease occurred in 42 patients (33.8%) and 2 patients (1.6%) experienced relapse within 6 months. The univariate analysis on refractory disease status shows age (p = 0.009), Ann Arbor stage (p = 0.013), CMV infection (p = 0.012), comorbidity (p = 0.019), IPI score (p<0.001), first line of treatment (p<0.001), EBV infection (p = 0.008) and socio-economics status (p = 0.02) as influencing factors. The NB Categorical classifier emerged as the top-performing model, boasting a ROC-AUC of 0.81 (95% CI, 0.64–0.96), an accuracy of 83%, a F1-score of 0.82, and a low false positive rate at 10% on the validation set. The eXtreme Gradient Boost (XGboost) model and the Random Forest Classifier (RFC) followed with a ROC-AUC of 0.74 (95%CI, 0.52–0.93) and 0.67 (95%CI, 0.46–0.88) respectively, an accuracy of 78% and 72% respectively, a F1-score of 0.75 and 0.67 respectively, and a false positive rate of 10% for both. The other two models performed worse with ROC-AUC of 0.65 (95%CI, 0.40–0.87) and 0.45 (95%CI, 0.29–0.64) for SVM and LR respectively, an accuracy of 67% and 50% respectively, a f1-score of 0.64 and 0.43 respectively, and a false positive rate of 28% and 37% respectively. Conclusion: Machine learning algorithms, particularly the NB Categorical classifier, have the potential to improve the prediction of primary refractory disease in DLBCL patients, thereby providing a novel decision-making tool for managing this condition. To validate these results on a broader scale, multicenter studies are needed to confirm the results in larger cohorts. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor published in the journal Leukemia & Lymphoma. It discusses three cases of tumor flare, a localized inflammatory response, in patients with non-Hodgkin lymphoma who received glofitamab, a T-cell-engaging bispecific monoclonal antibody. The cases range from mild to life-threatening, and multidisciplinary evaluation is recommended when the tumor site is near a vital organ. The authors suggest that ongoing treatment with T-cell-engaging bispecific antibodies may be feasible and beneficial for patients with no other treatment options. [Extracted from the article]

Purpose: Hepatic fibrosis develops as a response to chronic liver injury, resulting in the formation of fibrous scars. This process is initiated and driven by collagen-producing activated myofibroblasts which reportedly express high levels of platelet derived growth factor receptor-β (PDGFRβ). We therefore regard PDGFRβ as an anchor for diagnosis and therapy. The Fibrobody® SP02SP26-ABD is a biparatopic VHH-construct targeting PDGFRβ. Here, we explore its potential as a theranostic vector for liver fibrosis. Methods: Specificity, cross-species binding, and cellular uptake of SP02SP26-ABD was assessed using human, mouse and rat PDGFRβ ectodomains and PDGFRβ-expressing cells. Cellular uptake by PDGFRβ-expressing cells was also evaluated by equipping the Fibrobody® with auristatinF and reading out in vitro cytotoxicity. The validity of PDGFRβ as a marker for active fibrosis was confirmed in human liver samples and 3 mouse models of liver fibrosis (DDC, CCl4, CDA-HFD) through immunohistochemistry and RT-PCR. After radiolabeling of DFO*-SP02SP26-ABD with 89Zr, its in vivo targeting ability was assessed in healthy mice and mice with liver fibrosis by PET-CT imaging, ex vivo biodistribution and autoradiography. Results: SP02SP26-ABD shows similar nanomolar affinity for human, mouse and rat PDGFRβ. Cellular uptake and hence subnanomolar cytotoxic potency of auristatinF-conjugated SP02SP26-ABD was observed in PDGFRβ-expressing cell lines. Immunohistochemistry of mouse and human fibrotic livers confirmed co-localization of PDGFRβ with markers of active fibrosis. In all three liver fibrosis models, PET-CT imaging and biodistribution analysis of [89Zr]Zr-SP02SP26-ABD revealed increased PDGFRβ-specific uptake in fibrotic livers. In the DDC model, liver uptake was 12.15 ± 0.45, 15.07 ± 0.90, 20.23 ± 1.34, and 20.93 ± 4.35%ID/g after 1,2,3 and 4 weeks of fibrogenesis, respectively, compared to 7.56 ± 0.85%ID/g in healthy mice. Autoradiography revealed preferential uptake in the fibrotic (PDGFRβ-expressing) periportal areas. Conclusion: The anti-PDGFRβ Fibrobody® SP02SP26-ABD shows selective and high-degree targeting of activated myofibroblasts in liver fibrosis, and qualifies as a vector for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

A recent article in the European Journal of Nuclear Medicine & Molecular Imaging discusses the use of [18F]Fluorocholine PET/CT as a first-line imaging method for localizing parathyroid adenomas in primary hyperparathyroidism. The article emphasizes the importance of considering multiple domains, including technical capacity, diagnostic performance, clinical impact, influence on patient outcome, and cost-effectiveness, when evaluating diagnostic tests. The authors present the results of a cost-effectiveness analysis comparing a one-stop-shop imaging strategy with current standard imaging methods and conclude that first-line [18F]Fluorocholine PET/CT can be cost-effective in Europe and should be integrated into routine clinical practice. The findings suggest that [99mTc]Tc-MIBI scan may become obsolete in primary hyperparathyroidism if [18F]Fluorocholine PET/CT is available. [Extracted from the article]

The article focuses on the case of a 5-year-old girl presenting with unintentional weight loss and abdominal distension, which led to the discovery of ascites and other concerning findings. Topics include her travel history and potential exposure risks, the diagnostic workup including imaging and laboratory results, and the clinical presentation of her condition.

Background: Aneurysms of the internal iliac artery in infective endocarditis are extremely rare, with few cases reported in the literature, and Rothia dentocariosa infective endocarditis are rare. Analysis: We describe the case of a previously healthy 62-year-old male who presented a Rothia dentocariosa infective endocarditis. Results: Multi-modality imaging revealed an aneurysm of the left internal iliac artery, which was clinically silent. The patient was treated with antibiotics and semi-emergent bioprosthesis aortic valve replacement. Follow-up multi-modality imaging showed the regression of the aneurysm. Conclusion: This case shows that an aneurysm of the internal iliac artery in infective endocarditis can regress under antibiotherapy alone. This case also highlights the ability of PET/CT to identify and follow such an aneurysm. [ABSTRACT FROM AUTHOR]

Background and Aims: Interdigitating dendritic cell tumour/sarcoma (IDCS) is an exceedingly uncommon and aggressive tumour with a dismal prognosis. IDCS arises from antigen-presenting cells, which involve nodal and extranodal sites. The aim of the study is to evaluate a case of IDCS and its diagnostic challenges. Methods: A 21-year-old female with no comorbidities, a bone marrow aspirate and biopsy and an excision biopsy of the lymph node shows atypical mononuclear infiltrates that were immunohistochemically positive for S100-diffuse, CD68, LCA and Ki67. Results: Here, we report a single case of IDCS with a tumour arising from the lymph node and bone marrow infiltration. Discussion: IDCS is an aggressive disease with uncertain behaviour; strong suspicion is required to establish a diagnosis. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients with advanced, well-differentiated neuroendocrine tumors (WD-NETs) often require both peptide receptor radionuclide therapy (PRRT) and subsequent chemotherapy. However, no mid-PRRT predictors are available to identify patients who will not benefit from subsequent PRRT to limit their radiation exposure. Our aim is to characterize patients for whom subsequent PRRT is less efficacious on the basis of mid-PRRT evaluation. MATERIALS AND METHODS: A retrospective study of patients with WD-NET who underwent ≥four PRRT cycles. Data gathered included demographics, tumor grade, stage, and response (partial response [PR], stable disease [SD], and progressive disease [PD]) on the basis of RECIST 1.1 criteria and 68Ga-dotatate positron emission tomography-computerized tomography pretreatment, after second and fourth treatment cycle, 6 months after fourth cycle, and at last follow-up. RESULTS: Fifty-one patients (51.6% women; age at diagnosis 66.0 ± 1.65 years), with pancreatic NET (PNET; n = 24), small intestine NET (n = 13), or other NET (n = 14), received PRRT, resulting in PR (n = 21), SD (n = 23), and PD (n = 3). Of the patients reaching PR after PRRT, most reached PR after two treatments (70.4%), with only 11.8% PR occurring between subsequent cycles (P =.001). Furthermore, patients with PR at mid-treatment had higher PR rates after PRRT completion than those with SD (P =.007). Patients harboring PNET who achieved PR had a more pronounced reduction of tumor burden in additional cycles than patients who did not (25.6% v 1.5%; P =.03, respectively). On the multivariable model, adjusted for grade and primary site, PR at mid-treatment evaluation was associated with a 20.9 adjusted odds ratio for additional PR at PRRT completion (P =.002). CONCLUSION: Mid-PRRT assessment predicts subsequent PRRT response in patients with WD-NET, especially those with PNET, informing personalized management and consideration of reduced bone marrow radiation exposure in high-risk patients. Limited response in 2 cycles of PRRT for NEN correlated with limited response in additional 2 cycles. [ABSTRACT FROM AUTHOR]

Purpose: PET/CT-based Deauville scoring (DS) is routinely used for lymphoma response assessment. However, pathological correlation of DS is not yet precisely documented. In the present study we aimed to pathological confirm the PET/CT-based Deauville scoring (DS) in lymphoma after first-line chemotherapy. Materials and methods: Participants undergoing PET/CT for response assessment following first-line treatment were recruited prospectively. DS ≥ 4 lesions were interpreted as PET-positive, while DS ≤ 3 as PET-negative. Participants with a PET-positive lesion or suspicious of inadequate response (DS ≤ 3) were recruited for metabolic core-needle biopsy. True-negative and benign histopathology were kept on follow-up for three months. Histopathological, clinical and imaging findings were assessed for diagnostic performance. Procedure-related complications were also noted. Results: In all, 148/480 participants were PET-positive, and 332/480 were PET-negative. 138/148 PET-positive and 12/332 PET-negative lesions were recruited for biopsy. Biopsy was performed in 147/150 participants (PET-positive 135; PET-negative 12). Three patients with inaccessible lesions were excluded. The diagnostic yield of the procedure was 97.3% (143/147). Histology revealed lymphoma in 106 participants (including 70% of total DS-4, 100% of DS-5a and 73.9% of DS-5b lesions), with three false-negative lesions. DS ≤ 3 lesions were true-negative except one diagnosed with lymphoma (8.3%) on follow-up. Non-lymphomatous malignancies (n = 5), granulomas (n = 12), non-specific inflammation (n = 9) and no residual disease (n = 11) were diagnosed in the rest. No major procedure-related adverse event was noted. Conclusion: A DS-5a lesion suggests residual disease; hence, a biopsy can be prevented unless Richter's transformation is suspected. DS-4 and DS-5b lesions require a biopsy before changing the treatment plan, as a certain number of participants had non-lymphomatous F-18 FDG-avid lesions. [ABSTRACT FROM AUTHOR]