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Abstract Background Composite hemangioendothelioma (CHE) is a rare intermediate-grade vascular tumor characterized by a complex histologic component. It occasionally metastasizes, but local recurrence is not uncommon. CHE is mainly located in the extremities’ distal dermis and subcutaneous soft tissues. It is rarely located in the bone. We report here two cases originally occurred in bone. Case presentation The first case of CHE occurred solely on the left pubis. The second case is a patient post-resection of CHE in the manubrium sterni 10 years ago [1], who presented with multiple lesions in the left ilium and T6, T12 vertebra. All these lesions in the two cases showed osteolytic bone destruction on computed tomography (CT) scans and showed relatively high signal intensity on the fat-suppressed sequences of T2-weighted magnetic resonance (MR) images and isointense signal intensity on T1-weighted MR images. After injection of contrast agent (Gd-DTPA), the lesions showed inhomogeneous enhancement. 2-deoxy-2 [F-18] fluoro-D-glucose positron emission tomography-computed tomography (18FDG PET-CT) showed increased FDG uptake in these osteolytic bone destruction areas with SUVmax around 5.0. Both patients underwent surgery. Lesions in the left pubis and left ilium were confirmed by postoperative pathology while lesions on the vertebrae were only biopsied, not surgically resected. The first patient had no recurrence or metastasis in 5 years after surgery. The second patient had surgery recently and is still being followed up. Conclusions CHE occurring in bone is rarely reported. Our report provides more detailed information on the diagnosis of CHE. Given that CHE is locally aggressive and occasionally metastatic, PET-CT may be helpful in staging and follow-up.

Abstract Background Coronavirus disease 2019 (COVID-19) patients initially develop respiratory symptoms, but they may also suffer from neurological symptoms. People with long-lasting effects after acute infections with severe respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., post-COVID syndrome or long COVID, may experience a variety of neurological manifestations. Although we do not fully understand how SARS-CoV-2 affects the brain, neuroinflammation likely plays a role. Methods To investigate neuroinflammatory processes longitudinally after SARS-CoV-2 infection, four experimentally SARS-CoV-2 infected rhesus macaques were monitored for 7 weeks with 18-kDa translocator protein (TSPO) positron emission tomography (PET) using [18F]DPA714, together with computed tomography (CT). The baseline scan was compared to weekly PET–CTs obtained post-infection (pi). Brain tissue was collected following euthanasia (50 days pi) to correlate the PET signal with TSPO expression, and glial and endothelial cell markers. Expression of these markers was compared to brain tissue from uninfected animals of comparable age, allowing the examination of the contribution of these cells to the neuroinflammatory response following SARS-CoV-2 infection. Results TSPO PET revealed an increased tracer uptake throughout the brain of all infected animals already from the first scan obtained post-infection (day 2), which increased to approximately twofold until day 30 pi. Postmortem immunohistochemical analysis of the hippocampus and pons showed TSPO expression in cells expressing ionized calcium-binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and collagen IV. In the hippocampus of SARS-CoV-2 infected animals the TSPO+ area and number of TSPO+ cells were significantly increased compared to control animals. This increase was not cell type specific, since both the number of IBA1+TSPO+ and GFAP+TSPO+ cells was increased, as well as the TSPO+ area within collagen IV+ blood vessels. Conclusions This study manifests [18F]DPA714 as a powerful radiotracer to visualize SARS-CoV-2 induced neuroinflammation. The increased uptake of [18F]DPA714 over time implies an active neuroinflammatory response following SARS-CoV-2 infection. This inflammatory signal coincides with an increased number of TSPO expressing cells, including glial and endothelial cells, suggesting neuroinflammation and vascular dysregulation. These results demonstrate the long-term neuroinflammatory response following a mild SARS-CoV-2 infection, which potentially precedes long-lasting neurological symptoms.

Merkel cell carcinoma (MCC) has a tendency for lymphatic spread and locoregional recurrence, although there is little data examining the risk factors for patients with lymph node-positive extremity lesions. The purpose of the current study was to examine the outcomes and risk factors associated with nodal metastasis in extremity MCC. We retrospectively reviewed the medical record of 120 patients with extremity MCC evaluated at our institution between 1994 and 2021. The mean age of this cohort was 71 years; 33% of patients were female; and 98% were Caucasian. Seventy-eight (65%) patients presented with localized disease. Thirty-seven (31%) patients had stage III disease, and five (4%) patients had stage IV disease. Treatment of primary lesions consisted primarily of margin-negative excision and adjuvant radiotherapy. Nodal metastases were most treated with adjuvant radiation or completion lymph node dissection. Five-year disease-specific survival in our series was 88% for patients with localized disease, 89% for stage IIIa disease, 40% for stage IIIb disease and 42% for stage IV. Factors associated with worse survival included immunosuppression and macroscopic nodal disease. In conclusion, extremity MCC has a low rate of local recurrence when treated with margin-negative excision and adjuvant radiation. However, treatment of nodal metastases remains a challenge with high rates of recurrence and mortality, particularly for patients who are immunosuppressed or who have macroscopic nodal disease.

Abstract Background This study evaluated, as a snapshot, the variability in quantification and image quality (IQ) of the clinically utilized PET [18F]FDG whole-body protocols in Finland using a NEMA/IEC IQ phantom permanently filled with 68Ge. Methods The phantom was imaged on 14 PET-CT scanners, including a variety of models from two major vendors. The variability of the recovery coefficients (RCmax, RCmean and RCpeak) of the hot spheres as well as percent background variability (PBV), coefficient of variation of the background (COVBG) and accuracy of corrections (AOC) were studied using images from clinical and standardized protocols with 20 repeated measurements. The ranges of the RCs were also compared to the limits of the EARL 18F standards 2 accreditation (EARL2). The impact of image noise on these parameters was studied using averaged images (AVIs). Results The largest variability in RC values of the routine protocols was found for the RCmax with a range of 68% and with 10% intra-scanner variability, decreasing to 36% when excluding protocols with suspected cross-calibration failure or without point-spread-function (PSF) correction. The RC ranges of individual hot spheres in routine or standardized protocols or AVIs fulfilled the EARL2 ranges with two minor exceptions, but fulfilling the exact EARL2 limits for all hot spheres was variable. RCpeak was less dependent on averaging and reconstruction parameters than RCmax and RCmean. The PBV, COVBG and AOC varied between 2.3–11.8%, 9.6–17.8% and 4.8–32.0%, respectively, for the routine protocols. The RC ranges, PBV and COVBG were decreased when using AVIs. With AOC, when excluding routine protocols without PSF correction, the maximum value dropped to 15.5%. Conclusion The maximum variability of the RC values for the [18F]FDG whole-body protocols was about 60%. The RC ranges of properly cross-calibrated scanners with PSF correction fitted to the EARL2 RC ranges for individual sphere sizes, but fulfilling the exact RC limits would have needed further optimization. RCpeak was the most robust RC measure. Besides COVBG, also RCs and PVB were sensitive to image noise.

Myocardial ischemia may induce myocardial fibrosis, a condition that progressively leads to ventricular remodeling, heightening the risk of heart failure. The timely detection of myocardial fibrosis is crucial for intervention and improved outcomes. 68Ga-FAPI-04 PET/CT shows promise in assessing fibroblast activation in patients with early myocardial infarction characterized by prolonged myocardial ischemia. However, there is a notable absence of data regarding patients with short-term myocardial ischemia, such as those experiencing unstable angina (UA). In this report, we evaluated a 49-year-old male with UA and severe stenosis in multiple coronary arteries using 68Ga-FAPI-04 PET/CT. The results demonstrated tracer-specific uptake (SUVmax = 4.6) in the left anterior descending artery (LAD) territory, consistent with myocardial anterior wall ischemia indicated by the electrocardiogram. Following vascular recanalization therapy and regular medication treatment, the patient remained free of angina recurrence. A subsequent review at 2 months revealed a significant reduction in myocardial tracer uptake (SUVmax = 1.8). This case illustrates the validity of 68Ga-FAPI-04 PET/CT in assessing the extent of early myocardial fibroblast activation in patients with UA. This approach offers valuable insights for early detection and visual evidence, providing information on disease progression and treatment response.

ABSTRACTBetter biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7–14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = −0.93, p = 0.022). Additionally, responders showed decreased and progressors increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8+ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS.

Purpose: This study was conducted to predict the lymph node status and survival of esophageal squamous cell carcinoma before treatment by PET-CT-related parameters. Methods: From January 2013 to July 2018, patients with pathologically diagnosed ESCC at our hospital were retrospectively enrolled. Completed esophagectomy and two- or three-field lymph node dissections were conducted. Those with neoadjuvant therapy were excluded. The first 65% of patients in each year were regarded as the training set and the last 35% as the test set. Nomogram was constructed by the "rms" package. Five-year, overall survival was analyzed based on the best cutoff value of risk score determined by the "survivalROC" package. Results: Ultimately, 311 patients were included with 209 in the training set and 102 in the test set. The positive rate of the lymph node in the training set was 36.8% and that in the test set was 32.4%. The C-index of the training set was 0.763 and the test set was 0.766. The decision curve analysis showed that it was superior to the previous methods based on lymph node uptake or long/short axis diameter or axial ratio. Risk score > 0.20 was significantly associated with 5-year, overall survival (p = 0.0015) in all patients. Conclusions: The nomogram constructed from PET-CT parameters including primary tumor metabolic length and thickness can accurately predict the risk of lymph node metastasis in ESCC. The risk score calculated by our model accurately predicts the patient's 5-year overall survival. [ABSTRACT FROM AUTHOR]

Simple Summary: In melanoma, distant metastasis is frequent. To assess the state of metastasis formation at diagnosis, a common method employed is an invasive sentinel lymph node biopsy. However, in recent years, the use of non-invasive positron emission tomography combined with computed tomography (PET/CT) imaging for primary staging, especially in thick primary melanoma, has significantly increased. This study aims to elucidate the value of whole-body imaging for staging at melanoma diagnosis and to identify when whole-body imaging is currently used for primary staging, as well as evaluating its diagnostic precision. Furthermore, its effects on the subsequent diagnostic and therapeutic procedures should be determined to better understand the possible future implications. Background: Melanoma staging at diagnosis predominantly depends on the tumor thickness. Sentinel lymph node biopsy (SLNB) is a common tool for primary staging. However, for tumors of >4 mm with ulceration, 3D whole-body imaging and, in particular, Fluor-18-Deoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT), is recommended beforehand. This study aimed to investigate the real-world data of whole-body imaging for initial melanoma staging and its impact on the subsequent diagnostic and therapeutic procedures. Methods: In this retrospective single-center study, 94 patients receiving 18F-FDG-PET/CT and six patients with whole-body computed tomography (CT) scans were included. The clinical characteristics, imaging results, and histologic parameters of the primary tumors and metastases were analyzed. Results: Besides the patients with primary tumors characterized as pT4b (63%), the patients with pT4a tumors and pT3 tumors close to 4 mm in tumor thickness also received initial whole-body imaging. In 42.6% of the patients undergoing 18F-FDG-PET/CT, the imaging results led to a change in the diagnostic or therapeutic procedure following on from this. In 29% of cases, sentinel lymph node biopsy was no longer necessary. The sensitivity and specificity of 18F-FDG-PET/CT were 66.0% and 93.0%, respectively. Conclusion: Whole-body imaging as a primary diagnostic tool is highly valuable and influences the subsequent diagnostic and therapeutic procedures in a considerable number of patients with a relatively high tumor thickness. It can help avoid the costs and invasiveness of redundant SLNB and simultaneously hasten the staging of patients at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Artificial intelligence (AI) has seamlessly integrated into the medical field, especially in diagnostic imaging, thanks to ongoing AI advancements. It is widely used in various medical applications. In the context of breast cancer (BC), machine learning and deep learning are extensively employed for automating diagnosis, segmenting relevant data, and predicting pre-treatment tumor response to new adjuvant chemotherapy (NAC). Recent research has shown promising results with deep learning algorithms in BC diagnosis, accurately identifying specific features, demonstrating AI's potential to enhance BC diagnosis and analysis precision and efficiency. Additionally, utilizing non-ionized modalities, apart from ionized mammograms, has a substantial impact on the diagnosis process. Breast cancer stands out as the most frequently identified malignancy, ranking as the fifth leading cause of global cancer-related deaths. The American College of Radiology (ACR) introduced the Breast Imaging Reporting and Data System (BI-RADS) as a standard terminology facilitating communication between radiologists and clinicians; however, an update is now imperative to encompass the latest imaging modalities developed subsequent to the 5th edition of BI-RADS. Within this review article, we provide a concise history of BI-RADS, delve into advanced mammography techniques, ultrasonography (US), magnetic resonance imaging (MRI), PET/CT images, and microwave breast imaging, and subsequently furnish comprehensive, updated insights into Molecular Breast Imaging (MBI), diagnostic imaging biomarkers, and the assessment of treatment responses. This endeavor aims to enhance radiologists' proficiency in catering to the personalized needs of breast cancer patients. Lastly, we explore the augmented benefits of artificial intelligence (AI), machine learning (ML), and deep learning (DL) applications in segmenting, detecting, and diagnosing breast cancer, as well as the early prediction of the response of tumors to neoadjuvant chemotherapy (NAC). By assimilating state-of-the-art computer algorithms capable of deciphering intricate imaging data and aiding radiologists in rendering precise and effective diagnoses, AI has profoundly revolutionized the landscape of breast cancer radiology. Its vast potential holds the promise of bolstering radiologists' capabilities and ameliorating patient outcomes in the realm of breast cancer management. [ABSTRACT FROM AUTHOR]

We performed a systematic evaluation of the diagnostic performance of LAFOV PET/CT with increasing acquisition time. The first 100 oncologic adult patients referred for 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose PET/CT on the Siemens Biograph Vision Quadra were included. A standard imaging protocol of 10 min was used and scans were reconstructed at 30 s, 60 s, 90 s, 180 s, 300 s, and 600 s. Paired comparisons of quantitative image noise, qualitative image quality, lesion detection, and lesion classification were performed. Image noise (n = 50, 34 women) was acceptable according to the current standard of care (coefficient-of-varianceref < 0.15) after 90 s and improved significantly with increasing acquisition time (PB < 0.001). The same was seen in observer rankings (PB < 0.001). Lesion detection (n = 100, 74 women) improved significantly from 30 s to 90 s (PB < 0.001), 90 s to 180 s (PB = 0.001), and 90 s to 300 s (PB = 0.002), while lesion classification improved from 90 s to 180 s (PB < 0.001), 180 s to 300 s (PB = 0.021), and 90 s to 300 s (PB < 0.001). We observed improved image quality, lesion detection, and lesion classification with increasing acquisition time while maintaining a total scan time of less than 5 min, which demonstrates a potential clinical benefit. Based on these results we recommend a standard imaging acquisition protocol for LAFOV PET/CT of minimum 180 s to maximum 300 s after injection of 3 MBq/kg 2-[18F]fluoro-2-deoxy-D-glucose. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the uptake characteristics of 18F-fluoromisonidazole (FMISO), in mutant-type isocitrate dehydrogenase (IDH-mutant, grade 3 and 4) and wild-type IDH (IDH-wildtype, grade 4) 2021 WHO classification adult-type diffuse gliomas. Materials and methods: Patients with grade 3 and 4 adult-type diffuse gliomas (n = 35) were included in this prospective study. After registering 18F-FMISO PET and MR images, standardized uptake value (SUV) and apparent diffusion coefficient (ADC) were evaluated in hyperintense areas on fluid-attenuated inversion recovery (FLAIR) imaging (HIA), and in contrast-enhanced tumors (CET) by manually placing 3D volumes of interest. Relative SUVmax (rSUVmax) and SUVmean (rSUVmean), 10th percentile of ADC (ADC10pct), mean ADC (ADCmean) were measured in HIA and CET, respectively. Results: rSUVmean in HIA and rSUVmean in CET were significantly higher in IDH-wildtype than in IDH-mutant (P = 0.0496 and 0.03, respectively). The combination of FMISO rSUVmean in HIA and ADC10pct in CET, that of rSUVmax and ADC10pct in CET, that of rSUVmean in HIA and ADCmean in CET, were able to differentiate IDH-mutant from IDH-wildtype (AUC 0.80). When confined to astrocytic tumors except for oligodendroglioma, rSUVmax, rSUVmean in HIA and rSUVmean in CET were higher for IDH-wildtype than for IDH-mutant, but not significantly (P = 0.23, 0.13 and 0.14, respectively). The combination of FMISO rSUVmean in HIA and ADC10pct in CET was able to differentiate IDH-mutant (AUC 0.81). Conclusion: PET using 18F-FMISO and ADC might provide a valuable tool for differentiating between IDH mutation status of 2021 WHO classification grade 3 and 4 adult-type diffuse gliomas. [ABSTRACT FROM AUTHOR]

Background: The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment. Methods: Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale. Results: There was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients. Conclusions: Using the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients. [ABSTRACT FROM AUTHOR]

Background: The Q.Clear algorithm is a fully convergent iterative image reconstruction technique. We hypothesize that different PET/CT scanners with distinct crystal properties will require different optimal settings for the Q.Clear algorithm. Many studies have investigated the improvement of the Q.Clear reconstruction algorithm on PET/CT scanner with LYSO crystals and SiPM detectors. We propose an optimum penalization factor (β) for the detection of rectal cancer and its metastases using a BGO-based detector PET/CT system which obtained via accurate and comprehensive phantom and clinical studies. Methods: 18F-FDG PET-CT scans were acquired from NEMA phantom with lesion-to-background ratio (LBR) of 2:1, 4:1, 8:1, and 15 patients with rectal cancer. Clinical lesions were classified into two size groups. OSEM and Q.Clear (β value of 100–500) reconstruction was applied. In Q.Clear, background variability (BV), contrast recovery (CR), signal-to-noise ratio (SNR), SUVmax, and signal-to-background ratio (SBR) were evaluated and compared to OSEM. Results: OSEM had 11.5–18.6% higher BV than Q.Clear using β value of 500. Conversely, RC from OSEM to Q.Clear using β value of 500 decreased by 3.3–7.7% for a sphere with a diameter of 10 mm and 2.5–5.1% for a sphere with a diameter of 37 mm. Furthermore, the increment of contrast using a β value of 500 was 5.2–8.1% in the smallest spheres compared to OSEM. When the β value was increased from 100 to 500, the SNR increased by 49.1% and 30.8% in the smallest and largest spheres at LBR 2:1, respectively. At LBR of 8:1, the relative difference of SNR between β value of 100 and 500 was 43.7% and 44.0% in the smallest and largest spheres, respectively. In the clinical study, as β increased from 100 to 500, the SUVmax decreased by 47.7% in small and 31.1% in large lesions. OSEM demonstrated the least SUVmax, SBR, and contrast. The decrement of SBR and contrast using OSEM were 13.6% and 12.9% in small and 4.2% and 3.4%, respectively, in large lesions. Conclusions: Implementing Q.Clear enhances quantitative accuracies through a fully convergent voxel-based image approach, employing a penalization factor. In the BGO-based scanner, the optimal β value for small lesions ranges from 200 for LBR 2:1 to 300 for LBR 8:1. For large lesions, the optimal β value is between 400 for LBR 2:1 and 500 for LBR 8:1. We recommended β value of 300 for small lesions and β value of 500 for large lesions in clinical study. [ABSTRACT FROM AUTHOR]

Background: Preoperative stratification is critical for the management of patients with esophageal cancer (EC). To investigate the feasibility and accuracy of PET-CT-based radiomics in preoperative prediction of clinical and pathological stages for patients with EC. Methods: Histologically confirmed 100 EC patients with preoperative PET-CT images were enrolled retrospectively and randomly divided into training and validation cohorts at a ratio of 7:3. The maximum relevance minimum redundancy (mRMR) was applied to select optimal radiomics features from PET, CT, and fused PET-CT images, respectively. Logistic regression (LR) was applied to classify the T stage (T1,2 vs. T3,4), lymph node metastasis (LNM) (LNM(−) vs. LNM(+)), and pathological state (pstage) (I–II vs. III–IV) with features from CT (CT_LR_Score), PET (PET_LR_Score), fused PET/CT (Fused_LR_Score), and combined CT and PET features (CT + PET_LR_Score), respectively. Results: Seven, 10, and 7 CT features; 7, 8, and 7 PET features; and 3, 6, and 3 fused PET/CT features were selected using mRMR for the prediction of T stage, LNM, and pstage, respectively. The area under curves (AUCs) for T stage, LNM, and pstage prediction in the validation cohorts were 0.846, 0.756, 0.665, and 0.815; 0.769, 0.760, 0.665, and 0.824; and 0.727, 0.785, 0.689, and 0.837 for models of CT_LR_Score, PET_ LR_Score, Fused_ LR_Score, and CT + PET_ LR_Score, respectively. Conclusions: Accurate prediction ability was observed with combined PET and CT radiomics in the prediction of T stage, LNM, and pstage for EC patients. Critical relevance statement: PET/CT radiomics is feasible and promising to stratify stages for esophageal cancer preoperatively. Key points: • PET-CT radiomics achieved the best performance for Node and pathological stage prediction. • CT radiomics achieved the best AUC for T stage prediction. • PET-CT radiomics is feasible and promising to stratify stages for EC preoperatively. [ABSTRACT FROM AUTHOR]

In oligo-metastatic renal cell carcinoma (RCC), neither computed tomography (CT) nor bone scan is sensitive enough to detect small tumor deposits hampering early treatment and potential cure. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the neo-vasculature of numerous malignant neoplasms, including RCC, that can be targeted by positron emission tomography (PET) using PSMA-targeting radioligands. Our aim was to investigate whether PSMA-expression patterns of renal cancer in the primary tumor or metastatic lesions on immunohistochemistry (IHC) are associated with PET/CT findings using [68Ga]-PSMA-HBED-CC (PSMA-PET/CT). We then analyzed the predictive and prognostic role of the PSMA-PET/CT signal. In this retrospective single-center study we included patients with renal cancer submitted to PSMA-PET/CT for staging or restaging, with tumor specimens available for PSMA-IHC. Clinical information (age, tumor type, and grade) and IHC results from the primary tumor or metastases were collected. The intensity of PSMA expression at IHC was scored into four categories: 0: none; 1: weak; 2: moderate; 3: strong. PSMA expression was also graded according to the proportion of vessels involved (PSMA%) into four categories: 0: none; 1: 1–25%; 2: 25–50%; 3: >50%. The intensity of PSMA expression and PSMA% were combined in a three-grade score: 0–2 absent or mildly positive, 3–4 moderately positive, and 5–6 strongly positive. PSMA scores were used for correlation with PSMA-PET/CT results. Results: IHC and PET scans were available for the analysis in 26 patients (22 ccRCC, 2 papillary RCC, 1 chromophobe, 1 "not otherwise specified" RCC). PSMA-PET/CT was positive in 17 (65%) and negative in 9 patients (35%). The mean and median SUVmax in the target lesion were 34.1 and 24.9, respectively. Reporter agreement was very high for both distant metastasis location and local recurrence (kappa 1, 100%). PSMA-PET detected more lesions than conventional imaging and revealed unknown metastases in 4 patients. Bone involvement, extension, and lesion number were greater than in the CT scan (median lesion number on PET/CT 3.5). The IHC PSMA score was concordant in primary tumors and metastases. All positive PSMA-PET/CT results (15/22 ccRCC, 1 papillary cancer type II, and 1 chromofobe type) were revealed in tumors with strong or moderate PSMA combined scores (3–4 and 5–6). In ccRCC tissue samples, PSMA expression was strong to moderate in 20/22 cases. The SUVmax values correlated to the intensity of PSMA expression which were assessed using IHC (p = 0.01), especially in the ccRCC subgroup (p = 0.009). Median survival was significantly higher in patients with negative PSMA-PET/CT (48 months) compared to patients with a positive scan (24 months, p= 0.001). SUVmax ≥ 7.4 provides discrimination of patients with a poor prognosis. Results of PSMA-PET/CT changed treatment planning. Conclusions: in renal cancer, positive PSMA-PET/CT is strongly correlated to the intensity of PSMA expression on immunohistochemistry in both ccRCC and chromophobe cancer. PSMA-PET/CT signal predicts a poor prognosis confirming its potential as an aggressiveness biomarker and providing paramount additional information influencing patient management. [ABSTRACT FROM AUTHOR]

INTRODUCTION: 18F‐Fluoro‐deoxyglucose–positron emission tomography (FDG‐PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG‐PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis. METHODS: FDG‐PET scans were visually and semi‐quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi‐quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features. RESULTS: At follow‐up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi‐quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%). DISCUSSION: FDG‐PET is a valuable tool in DLB diagnosis, having visual and semi‐quantitative analyses with the highest diagnostic accuracy at ML analyses. [ABSTRACT FROM AUTHOR]

We review the rationale, methodology, and clinical utility of quantitative [18F] sodium fluoride ([18F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (Ki, also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [18F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [18F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is more common in men aged 40 to 59, and radiotherapy is an effective treatment. Nasopharyngeal lymphoma (NPL) is rare, and the coexistence of nasopharyngeal mantle cell lymphoma (MCL) and NPC is even rarer. A collision tumor is a rare type of tumor that refers to two or more different tumors occurring in the same organ. No reports to date have described a collision tumor of NPC and MCL occurring within the same nasopharyngeal mass. We herein report the successful treatment of a unique case of synchronous coexistence of NPC and MCL occurring in the nasopharynx of a Chinese man. Case presentation: A 58-year-old man presented with a 5-month history of swallowing discomfort. Biopsy was performed under nasopharyngeal endoscopy, and histopathology revealed NPC. Magnetic resonance imaging revealed lesions in the nasopharynx, oropharynx, and tonsils, as well as enlarged lymph nodes in the parotid gland, posterior ear, and neck. This may be a synchronous dual primary tumor coexisting with NPC and NPL. Pathology consultation confirmed that the biopsy specimen of the nasopharynx was a collision tumor of NPC and MCL. Positron emission tomography computed tomography (PET-CT) revealed thickening of the posterior wall of the nasopharynx, which was considered NPC with lymphoma. The enlargement of the pharyngeal lymph ring and multiple hypermetabolic lymph nodes were evaluated as lymphoma infiltration. The patient received two courses of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by head and neck radiotherapy. At the time of this writing, he had remained alive without recurrence for 61 months since the initial treatment and was still undergoing follow-up. Conclusions: It is very important to correctly recognize collision tumors. Magnetic resonance imaging helps identify different components of collision tumors. Pathological examination helps to confirm the diagnosis. Histological examination reveals different components, and PET-CT can help determine the extent of the lesion. Dose-adjusted chemotherapy combined with radiotherapy may have promising herapeutic effects, but additional case studies are needed to confirm. [ABSTRACT FROM AUTHOR]

Background: Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant 89Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; FcγR). After antibody injection in mice harboring xenografts of different tumor cell lines or of immortalized human myoblasts, we analyzed antibody biodistribution by PET-CT and conventional biodistribution analysis. Results: Accumulation in liver was strongly reduced and tumor-specific targeting was increased for the antibodies with mutated Fc compared with wild-type Fc. Conclusion: Antibodies with reduced binding to FcγR display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches. [ABSTRACT FROM AUTHOR]

Radiologic imaging, especially MRI, has long been the mainstay for rectal cancer staging and patient selection for neoadjuvant therapy prior to surgical resection. In contrast, colonoscopy and CT have been the standard for colon cancer diagnosis and metastasis staging with T and N staging often performed at the time of surgical resection. With recent clinical trials exploring the expansion of the use of neoadjuvant therapy beyond the anorectum to the remainder of the colon, the current and future state of colon cancer treatment is evolving with a renewed interest in evaluating the role radiology may play in the primary T staging of colon cancer. The performance of CT, CT colonography, MRI, and FDG PET-CT for colon cancer staging will be reviewed. N staging will also be briefly discussed. It is expected that accurate radiologic T staging will significantly impact future clinical decisions regarding the neoadjuvant versus surgical management of colon cancer. [ABSTRACT FROM AUTHOR]

Prostatic neuroendocrine malignancies represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine tumors (P-NETs) and carcinomas (P-NECs). While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects cellular glucose metabolism, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and prostate-specific membrane antigen (PSMA)-ligands labeled with either 18F or 68Ga, are now routinely used in departments of nuclear medicine and molecular imaging, and may be advantageous in imaging prostatic neuroendocrine malignancies. Still, the selection of the preferred PET radiotracer in such cases might be challenging. In the current review, we summarize and discuss published data on these different entities from clinical, biological, and molecular imaging standpoints. Specifically, we review the roles that [18F]FDG, radiolabeled somatostatin-analogues, and radiolabeled PSMA-ligands play in these entities in order to provide the reader with practical recommendations regarding the preferred PET radiotracers for imaging each entity. In cases of tiNED, we conclude that PSMA expression may be low and that [18F]FDG or radiolabeled somatostatin-analogues should be preferred for imaging. In cases of prostatic adenocarcinoma with dNED, we present data that support the superiority of radiolabeled PSMA-ligands. In cases of primary neuroendocrine malignancies, the use of [18F]FDG for imaging high-grade P-NECs and radiolabeled somatostatin-analogues for imaging well-differentiated P-NETs is recommended. Key Points: • The preferred PET radiotracer for imaging prostatic neuroendocrine malignancies depends on the specific clinical scenario and pathologic data. • When neuroendocrine features result from hormonal therapy for prostate cancer, PET-CT should be performed with [18F]FDG or radiolabeled somatostatin-analogue rather than with radiolabeled PSMA-ligand. • When neuroendocrine features are evident in newly diagnosed prostate cancer, differentiating adenocarcinoma from primary neuroendocrine malignancy is challenging but crucial for selection of PET radiotracer and for clinical management. [ABSTRACT FROM AUTHOR]

Background Flourine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) is a well-established imaging modality for the evaluation of patients with oncological and nononcological conditions. The underlying principle of imaging is the preferentially increased glucose consumption by cancer cells, due to overexpression of glucose type 1 receptors that are insulin independent. Thus, one of the factors that leads to decreased sensitivity of an 18 F-FDG PET-CT is elevated blood sugar levels, leading to decreased glucose uptake by cancer cells due to competitive inhibition. A significant percentage of patients scheduled for PET-CT scan has diabetes mellitus type II as a comorbid condition and often has elevated random blood sugar (RBS) precluding an upfront PET-CT evaluation. Such cases must be rescheduled. This causes delay in the evaluation and management of such patients. Empagliflozin is a novel sodium glucose type 2 inhibitor that prevents tubular reabsorption of glucose and increases renal glycosuria resulting in decreased blood sugar. This drug does not cause significant hypoglycemia or increase endogenous insulin secretion. This study was undertaken to evaluate a potential role for empagliflozin in facilitating optimal blood sugar control in patients with hyperglycemia on the day of the scheduled PET scan. Methods This is an interventional prospective study and patients detected to have RBS more than 200 mg/dL on the day of the scheduled scan were included in the study. The patients were administered two tablets of 10 mg empagliflozin and kept under observation. Samples for RBS were taken at approximately 2nd and 4th hour post administration by bedside method. These patients underwent scan on the same day after adequate sugar control and when an RBS of less than 200 mg/dL was achieved. The primary outcome studied was change in RBS values in the patient cohort and evaluation of PET SUV (standardized uptake value) compared with the rest of the patients scheduled on the same day. Secondary outcome was assessment of any side effects in the patients. Results Total of 10 patients were found to have elevated blood sugar (RBS > 200 mg/dL; irrespective of being on medication) and did not meet the evaluation criteria for a PET-CT scan on the scheduled day. Following administration of the drug, all 10 patients were able to attain blood sugar levels and fulfill the criteria for undergoing a PET-CT scan. No obvious side effect was noted in any of the patient. The SUV values of the patient cohort were comparable with the rest of the patient scanned on the day. Conclusion In this pilot study, 20 mg of empagliflozin (2 tablets of 10 mg) appears to be a safe and effective method for achieving optimal decrease in the RBS without causing hypoglycemia or hyperinsulinemia. It can be safely employed in the subset of population with RBS between 201 and 300 mg/dL to adequately bring the sugar levels at acceptable levels RBS less than 200 mg/dl and fulfill the FDG PET-CT criteria as per European Association of Nuclear Medicine (EANM) norms. [ABSTRACT FROM AUTHOR]

To investigate the diagnostic value of Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (18F-FDG PET/CT) dual-phase imaging for the different molecular subtypes of invasive ductal carcinoma of the breast. Clinical imaging data of 164 women with invasive ductal carcinoma of the breast confirmed by pathology who underwent 18F-FDG PET/CT dual-phase imaging were retrospectively analyzed. The maximum standard uptake values (SUVmax) of the early and delayed phases of the lesion were measured and recorded as SUVmax1 and SUVmax2, respectively, and the retention index (RI) was calculated. We analyzed the change rule of SUVmax1, SUVmax2, and RI for the different molecular subtypes and molecular marker expression groups. The diagnostic threshold of different molecular marker expression status was determined using receiver operating characteristic curve analysis. SUVmax1 and SUVmax2 were highest in the TNBC group and lowest in the luminal A group (p <0.001). TNBC and HER2 overexpression groups had higher RI than the luminal A and B groups (p <0.001), with no significant difference between the TNBC and HER2 overexpression groups or between the luminal A and B groups (p =0.640 and 0.345, respectively). The ER- and PR-negative groups had significantly higher SUVmax1, SUVmax2, and RI than the PR-positive group (p <0.001). The HER2-positive group had higher SUVmax1 and SUVmax2 than the negative group (p <0.001). The Ki67 overexpression group had higher SUVmax1 and SUVmax2 levels than the low expression group (p <0.001). There was no significant difference in RI between HER2-positive and negative groups or between Ki67 high and low expression groups (p =0.904 and 0.216, respectively). For ER-negative and positive expression status, the maximum area under the curve (AUC) of SUVmax2 was 0.852, diagnostic threshold was 10.87, sensitivity was 79.6%, and specificity was 74.5%. For PR-negative and positive expression status, the AUC of SUVmax2 was 0.858, diagnostic threshold was 10.45, sensitivity was 83.1%, and specificity was 75.3%. For HER2-negative and positive expression status, the AUC of SUVmax1 was 0.714, diagnostic threshold was 9.28, sensitivity was 79.6%, and specificity was 60.9%. For Ki67 high- and low expression status, the AUC of SUVmax2 was 0.915 at maximum, diagnostic threshold was 10.21, sensitivity was 83.4%, and specificity was 93.9%. 18F-FDG PET/CT dual-phase imaging facilitates the prediction of the expression of molecular markers and subtypes of invasive ductal carcinoma of the breast and the development of more tailored treatment plans for patients with this disease. [ABSTRACT FROM AUTHOR]

A 67-year-old man had a tumor on his right cheek. It was resected 15 years earlier but recurred 1 year before his first visit. He had a red papule on his right cheek and subcutaneous induration in the right preauricular area. A right cheek biopsy revealed a mucinous carcinoma. The positron emission tomography-computed tomography showed accumulation only in the right cheek and parotid gland lymph node; therefore, we diagnosed primary cutaneous mucinous carcinoma. Sentinel lymphoscintigraphy showed accumulation of parotid gland and level II lymph node. He underwent extended resection and sentinel-node biopsy. Both lymph nodes were metastatic, requiring the appropriate range of neck dissection. There were no recurrence and metastasis postoperatively. There is no effective treatment when distant metastasis occurs, and the prognosis is poor. Therefore, it is important to prevent metastasis. However, positron emission tomography-computed tomography could not reveal early micrometastases. Therefore, a sentinel-node biopsy can be key to early detection and treatment.

Chimeric antigen receptor T-cell (CAR-T) therapy targeted against B-cell maturation antigen (BCMA) in multiple myeloma (MM) has produced rapid responses but many eventually relapse. In light of this new treatment, novel predictors of progression-free survival (PFS) are needed. We performed a single institution analysis of 54 BCMA-CAR-T patients. We analyzed patient's overall response rate (ORR) by the IMWG criteria, involved serum-free light chains (iFLC), and minimal residual disease testing by next-generation sequencing (MRD-NGS). Between patients who achieved a ≤SD and those who achieved a ≥PR, PFS differed significantly (p < 0.0001); though there was no difference between patients who achieved a ≥CR vs. VGPR/PR (p = 0.2). In contrast, patients who achieved a nonelevated iFLC at 15 days (p < 0.0001, HR = 6.8; 95% CI, 2.7-17.3) or 30 days (p < 0.001, HR = 16.7; 95% CI, 3.9-71.7) had a prolonged PFS compared with those with an elevated iFLC. Patients achieving MRD-NGS less than the detectable limit at a sensitivity of 10-6 had a better PFS than those with detectable disease at 1 month (p = 0.02) and 3 months (p = 0.02). In conclusion, achieving a nonelevated iFLC and an undetectable MRD-NGS quickly were factors that were strongly associated with improved PFS. Further studies are needed to confirm the role of these markers in MM patients receiving CAR-T therapies.

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

Background: Although positron emission tomography combined with computed tomography (PET-CT) plays an important role in detecting various types of childhood malignancy, it has low positive predictive value, owing to the nonspecific uptake of 18F-fluorodeoxyglucose (FDG) by normal tissue in various benign conditions. Case summary: A 5-year-old male patient with a malignant rhabdoid tumor originating in the left neck underwent primary tumor resection concurrently with ipsilateral lymph node dissection after receiving neoadjuvant chemotherapy consisting of cyclophosphamide, carboplatin, etoposide, vincristine, and doxorubicin. He later received the same adjuvant chemotherapy as well as proton therapy for the primary tumor. Sixteen months after completing the initial therapy, follow-up PET-CT revealed a novel area of glucose hypermetabolism in the right side of the tongue, which was suspected of being a recurrence. However, a physical examination and magnetic resonance imaging (MRI) demonstrated no evidence of tumor recurrence. The patient had a significant leftward deviation of the tongue, suggesting left hypoglossal nerve paralysis. Denervation of the ipsilateral intrinsic tongue muscles secondary to the treatment had caused atrophy in the ipsilateral muscles and compensatory hypertrophy in the contralateral muscles, which increased FDG uptake. Physicians should carefully confirm any diagnosis of a locally recurrent tumor because PET-CT often produces ambiguous findings.

Background: Correct staging and risk stratification is essential in ensuring prostate cancer patients are offered the most appropriate treatment. Interest has been growing in the use of radiotracers targeting prostate specific membrane antigen (PSMA), including the use of 18F-PSMA PET-CT, as part of the primary staging or restaging of prostate cancer. Preliminary scoping identified a number of relevant systematic reviews and meta-analyses; however, individually, these each appear to look at only part of the picture. An overview of reviews aims to systematically identify, appraise and synthesise multiple systematic reviews, related to a relevant research question or questions. We present a protocol for an overview of reviews, which aims to collate existing evidence syntheses exploring the diagnostic accuracy of 18F-PSMA in staging and restaging of prostate cancer. It also aims to highlight evidence gaps in prostate cancer staging or restaging. Methods: This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for systematic review protocols (PRISMA-P). The search strategy will be designed in consultation with a librarian. Searches will be performed in Medline (EBSCO), Embase (Ovid), Google Scholar and the Cochrane Database for Systematic Reviews, supplemented by a targeted grey literature search, forward citation searching and searching reference lists of included reviews. No language or date restrictions will be applied to the eligibility criteria or the search strategy. Title & abstract and full text screening will be performed independently by two reviewers. Data will be extracted by one reviewer and checked in full by a second reviewer. Quality appraisal will be performed using the Risk of Bias in Systematic Reviews (ROBIS) tool independently by two reviewers, and results will be narratively synthesised. Conclusions: This overview of reviews may be of interest to healthcare professionals, academics and health policy decision-makers. Registration: OSF (September 7, 2023).

Objective: Gallbladder cancer (GBC) typically follows an aggressive course with the standard of care for advanced disease; complete responses are rarely encountered. We report a case in which tumor disappearance on positron emission tomography computed tomography (PET-CT) was treated with S-1 as the second-line treatment for local recurrence of GBC after gemcitabine (GEM) plus cisplatin (CDDP) (GC) combination therapy. Case Presentation: A 69-year-old woman was referred to our hospital with complaints of right hypochondrial pain. Based on ultrasound, CT, and magnetic resonance imaging (MRI) findings, we diagnosed patient with suspected GBC. Results: We performed the resection of the gallbladder base, partial resection of the transverse colon, and partial resection of the stomach for GBC. At four months after the surgery, PET-CT showed local recurrence. First-line chemotherapy with GC therapy was initiated. After 9 courses, PET-CT showed increased local recurrence. We concluded that GC treatment was ineffective. Second-line chemotherapy with S-1 was initiated for two weeks, followed by a 7-day rest period. PET-CT in September 2019 showed the markedly reduction of the local recurrence, and PET-CT in October 2021 showed the complete disappearance of the local recurrence. At 20 months after the discontinuation of S-1, PET-CT showed the complete disappearance of the local recurrence. Conclusions: Chemotherapy with S-1 can be managed safely and was demonstrated to be effective in treating the local recurrence of GBC recurrence.

Background: Composite hemangioendothelioma (CHE) is a rare intermediate-grade vascular tumor characterized by a complex histologic component. It occasionally metastasizes, but local recurrence is not uncommon. CHE is mainly located in the extremities' distal dermis and subcutaneous soft tissues. It is rarely located in the bone. We report here two cases originally occurred in bone. Case presentation: The first case of CHE occurred solely on the left pubis. The second case is a patient post-resection of CHE in the manubrium sterni 10 years ago [1], who presented with multiple lesions in the left ilium and T6, T12 vertebra. All these lesions in the two cases showed osteolytic bone destruction on computed tomography (CT) scans and showed relatively high signal intensity on the fat-suppressed sequences of T2-weighted magnetic resonance (MR) images and isointense signal intensity on T1-weighted MR images. After injection of contrast agent (Gd-DTPA), the lesions showed inhomogeneous enhancement. 2-deoxy-2 [F-18] fluoro-D-glucose positron emission tomography-computed tomography (18FDG PET-CT) showed increased FDG uptake in these osteolytic bone destruction areas with SUVmax around 5.0. Both patients underwent surgery. Lesions in the left pubis and left ilium were confirmed by postoperative pathology while lesions on the vertebrae were only biopsied, not surgically resected. The first patient had no recurrence or metastasis in 5 years after surgery. The second patient had surgery recently and is still being followed up. Conclusions: CHE occurring in bone is rarely reported. Our report provides more detailed information on the diagnosis of CHE. Given that CHE is locally aggressive and occasionally metastatic, PET-CT may be helpful in staging and follow-up. [ABSTRACT FROM AUTHOR]

Thirty to 50% of differentiated thyroid carcinomas include papillary thyroid microcarcinomas (mPTC). Most of these tumors remain clinically silent, have a bright prognosis and a disease-specific mortality <1%. Surgery has been recommended as first line-treatment by current guidelines, the standard treatment being lobectomy. However, surgery has some drawbacks, including potential recurrent laryngeal nerve paralysis, hypothyroidism, hypoparathyroidism, in -patient basis hospital stay, lifelong medication, scarring of the neck, and general anesthesia related risks. Moreover, elderly patients who present severe comorbidities, could be ineligible for surgery, and others may refuse invasive surgery. Another option supported by the American Thyroid Association is active surveillance. This option can be considered as unattractive and difficult to accept by European patients, as there is a 2–6% risk of disease progression. Percutaneous image-guided thermal ablation has been successfully applied in the treatment of liver and lung tumors in the 1990s and 2000s; and has recently been proposed as an alternative to surgery in patients presenting with thyroid diseases. This minimally invasive treatment has similar efficacy, fewer complications, better quality of life and cosmetic outcomes than surgery. We report herein two cases of radiofrequency ablation of mPTC and T2 PTC in elderly patients who were ineligible for surgery. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) patients initially develop respiratory symptoms, but they may also suffer from neurological symptoms. People with long-lasting effects after acute infections with severe respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., post-COVID syndrome or long COVID, may experience a variety of neurological manifestations. Although we do not fully understand how SARS-CoV-2 affects the brain, neuroinflammation likely plays a role. Methods: To investigate neuroinflammatory processes longitudinally after SARS-CoV-2 infection, four experimentally SARS-CoV-2 infected rhesus macaques were monitored for 7 weeks with 18-kDa translocator protein (TSPO) positron emission tomography (PET) using [18F]DPA714, together with computed tomography (CT). The baseline scan was compared to weekly PET–CTs obtained post-infection (pi). Brain tissue was collected following euthanasia (50 days pi) to correlate the PET signal with TSPO expression, and glial and endothelial cell markers. Expression of these markers was compared to brain tissue from uninfected animals of comparable age, allowing the examination of the contribution of these cells to the neuroinflammatory response following SARS-CoV-2 infection. Results: TSPO PET revealed an increased tracer uptake throughout the brain of all infected animals already from the first scan obtained post-infection (day 2), which increased to approximately twofold until day 30 pi. Postmortem immunohistochemical analysis of the hippocampus and pons showed TSPO expression in cells expressing ionized calcium-binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and collagen IV. In the hippocampus of SARS-CoV-2 infected animals the TSPO+ area and number of TSPO+ cells were significantly increased compared to control animals. This increase was not cell type specific, since both the number of IBA1+TSPO+ and GFAP+TSPO+ cells was increased, as well as the TSPO+ area within collagen IV+ blood vessels. Conclusions: This study manifests [18F]DPA714 as a powerful radiotracer to visualize SARS-CoV-2 induced neuroinflammation. The increased uptake of [18F]DPA714 over time implies an active neuroinflammatory response following SARS-CoV-2 infection. This inflammatory signal coincides with an increased number of TSPO expressing cells, including glial and endothelial cells, suggesting neuroinflammation and vascular dysregulation. These results demonstrate the long-term neuroinflammatory response following a mild SARS-CoV-2 infection, which potentially precedes long-lasting neurological symptoms. [ABSTRACT FROM AUTHOR]

Background: Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) is listed in the World Health Organization (WHO) Classification 5th edition as a rare benign tumor with papillary growth of ciliary, goblet, and basal cells. Case presentation: The patient was a 67-year-old female in whom a nodular shadow of 20 mm in diameter in the right lower lobe S10 center was found in chest computed tomography (CT) for examination of dorsal pain. Positron emission tomography/computed tomography (PET-CT) showed the accumulation of 18F-fluorodeoxyglucose (FDG) with a standardized uptake value (SUV)max of 13.0. Primary lung cancer was suspected, and surgery was scheduled as a therapeutic strategy. Thoracoscopic resection of the right lower lobe was performed, and possible BA/CMPT or adenocarcinoma was suggested in the differential diagnosis by the intra-perioperative rapid pathologic diagnosis. The final diagnosis was BA/CMPT. Histological findings indicated that the cause of the high FDG-PET scan might be due to many inflammatory cell infiltration in the tumor. Conclusions: We report a resected case of BA/CMPT with exceptionally high FDG accumulation in PET. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of responses is critical in patients diagnosed with multiple myeloma. Nowadays, one of the most informative parameters to discriminate responses to treatment and prognosis is minimal residual disease (MRD). Several strategies may be used to detect and quantify MRD; some of them have been widely used and standardized, but we can find additional strategies lacking such an extensive validation process. Here, we present a summary of the current state of the art of MRD detection in multiple myeloma and future directions in the field. Responses to treatment have improved over the last decades for patients with multiple myeloma. This is a consequence of the introduction of new drugs that have been successfully combined in different clinical contexts: newly diagnosed, transplant-eligible or ineligible patients, as well as in the relapsed/refractory setting. However, a great proportion of patients continue to relapse, even those achieving complete response, which underlines the need for updated response criteria. In 2014, the international myeloma working group established new levels of response, prompting the evaluation of minimal residual disease (MRD) for those patients already in complete or stringent complete response as defined by conventional serological assessments: the absence of tumor plasma cells in 100,000 total cells or more define molecular and immunophenotypic responses by next-generation sequencing and flow cytometry, respectively. In this review, we describe all the potential methods that may be used for MRD detection based on the evidence found in the literature, paying special attention to their advantages and pitfalls from a critical perspective. [ABSTRACT FROM AUTHOR]

COVID-19 is a multisystemic disease, and hence its potential manifestations on nuclear medicine imaging can extend beyond the lung. Therefore, it is important for the nuclear medicine physician to recognize these manifestations in the clinic. While FDG-PET/CT is not indicated routinely in COVID-19 evaluation, its unique capability to provide a functional and anatomical assessment of the entire body means that it can be a powerful tool to monitor acute, subacute, and long-term effects of COVID-19. Single-photon scintigraphy is routinely used to assess conditions such as pulmonary embolism, cardiac ischemia, and thyroiditis, and COVID-19 may present in these studies. The most common nuclear imaging finding of COVID-19 vaccination to date is hypermetabolic axillary lymphadenopathy. This may pose important diagnostic and management dilemmas in oncologic patients, particularly those with malignancies where the axilla constitutes a lymphatic drainage area. This article aims to summarize the relevant literature published since the beginning of the pandemic on the intersection between COVID-19 and nuclear medicine. • Clinical and imaging manifestations of COVID-19 may occur outside of the respiratory tract and extend beyond the acute phase. • Evidence of inflammation involving any organ system should be carefully sought in patients with known or suspected COVID-19. • The most common nuclear imaging finding of COVID-19 vaccination is hypermetabolic axillary lymphadenopathy. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) has a tendency for lymphatic spread and locoregional recurrence, although there is little data examining the risk factors for patients with lymph node-positive extremity lesions. The purpose of the current study was to examine the outcomes and risk factors associated with nodal metastasis in extremity MCC. We retrospectively reviewed the medical record of 120 patients with extremity MCC evaluated at our institution between 1994 and 2021. The mean age of this cohort was 71 years; 33% of patients were female; and 98% were Caucasian. Seventy-eight (65%) patients presented with localized disease. Thirty-seven (31%) patients had stage III disease, and five (4%) patients had stage IV disease. Treatment of primary lesions consisted primarily of margin-negative excision and adjuvant radiotherapy. Nodal metastases were most treated with adjuvant radiation or completion lymph node dissection. Five-year disease-specific survival in our series was 88% for patients with localized disease, 89% for stage IIIa disease, 40% for stage IIIb disease and 42% for stage IV. Factors associated with worse survival included immunosuppression and macroscopic nodal disease. In conclusion, extremity MCC has a low rate of local recurrence when treated with margin-negative excision and adjuvant radiation. However, treatment of nodal metastases remains a challenge with high rates of recurrence and mortality, particularly for patients who are immunosuppressed or who have macroscopic nodal disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal masses represent a common incidental finding at imaging exams such as computed tomography (CT) and magnetic resonance imaging performed for unrelated reasons. Encompassing both benign and malignant entities, these lesions can prove challenging to classify. 2-[18F]FDG PET-CT is a recognized imaging modality for the characterization of indeterminate adrenal masses, but it is an expensive imaging modality and involves radiation exposure. To reduce the number of required scans and identify a less invasive potential alternative, we investigated whether CT radiomics could be used to predict the diagnostic parameter obtained using 2-[18F]FDG PET-CT (namely SUVmax). However, in our retrospective cohort of 179 adrenal masses and 150 PET-CT scans (of which 66 without iodine contrast injection), no correlation was found between the radiomics synthetic value (RadSV) and 2-[18F]FDG PET-CT SUVmax. This preliminary finding suggests that it might not be possible to use CT radiomics to reduce 2-[18F]FDG PET-CT referrals, confirming the role as problem solving tool of this imaging modality. Background: Indeterminate adrenal masses (AM) pose a diagnostic challenge, and 2-[18F]FDG PET-CT serves as a problem-solving tool. Aim of this study was to investigate whether CT radiomics features could be used to predict the 2-[18F]FDG SUVmax of AM. Methods: Patients with AM on 2-[18F]FDG PET-CT scan were grouped based on iodine contrast injection as CT contrast-enhanced (CE) or CT unenhanced (NCE). Two-dimensional segmentations of AM were manually obtained by multiple operators on CT images. Image resampling and discretization (bin number = 16) were performed. 919 features were calculated using PyRadiomics. After scaling, unstable, redundant, and low variance features were discarded. Using linear regression and the Uniform Manifold Approximation and Projection technique, a CT radiomics synthetic value (RadSV) was obtained. The correlation between CT RadSV and 2-[18F]FDG SUVmax was assessed with Pearson test. Results: A total of 725 patients underwent PET-CT from April 2020 to April 2021. In 150 (21%) patients, a total of 179 AM (29 bilateral) were detected. Group CE consisted of 84 patients with 108 AM (size = 18.1 ± 4.9 mm) and Group NCE of 66 patients with 71 AM (size = 18.5 ± 3.8 mm). In both groups, 39 features were selected. No statisticallyf significant correlation between CT RadSV and 2-[18F]FDG SUVmax was found (Group CE, r = 0.18 and p = 0.058; Group NCE, r = 0.13 and p = 0.27). Conclusions: It might not be feasible to predict 2-[18F]FDG SUVmax of AM using CT RadSV. Its role as a problem-solving tool for indeterminate AM remains fundamental. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma (DLBCL) is the most frequent aggressive lymphoma seen in clinical practice. Despite huge strides in understanding its biology, front‐line therapy has remained unchanged for decades. Roughly one‐third of patients have primary refractory or relapse following the end of conventional first‐line therapy. The outcome of patients with primary refractory disease and those with early relapse (defined as relapse less than 1 year from the end of therapy) is markedly inferior to those with later relapse and is exemplified by dismal overall survival. In this article, the authors term patients with features that identify them as being at particularly high‐risk for either primary refractory disease or early relapse, as 'ultra‐high‐risk'. As new treatment options become established (e.g. bispecific T‐cell engagers, chimeric antigen receptor 'CAR' T‐cells and antibody–drug conjugates), it is likely that there will be a push to incorporate some of these agents into the first‐line setting for patients identified as ultra‐high‐risk. In this review, the authors outline advances in positron emission tomography, widely available laboratory assays and clinical prognosticators, which can detect a high proportion of patients with ultra‐high‐risk disease. Since these approaches are pragmatic and able to be adopted widely, they could be incorporated into routine clinical practice. [ABSTRACT FROM AUTHOR]