International Benchmark for Total Metabolic Tumor Volume Measurement in Baseline 18F-FDG PET/CT of Lymphoma Patients: A Milestone Toward Clinical Implementation.

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark dataset allowing TMTV to be tested and applied as a reproducible biomarker. Methods: Sixty baseline 18F-FDG PET/CT scans were identified with a range of disease distributions (20 follicular, 20 Hodgkin, and 20 diffuse large B-cell lymphoma). TMTV was measured by 12 nuclear medicine experts, each analyzing 20 cases split across subtypes, with each case processed by 3-4 readers. LIFEx or ACCURATE software was chosen according to reader preference. Analysis was performed stepwise: TMTV1 with automated preselection of lesions using an SUV of at least 4 and a volume of at least 3 cm3 with single-click removal of physiologic uptake; TMTV2 with additional removal of reactive bone marrow and spleen with single clicks; TMTV3 with manual editing to remove other physiologic uptake, if required; and TMTV4 with optional addition of lesions using mouse clicks with an SUV of at least 4 (no volume threshold). Results: The final TMTV (TMTV4) ranged from 8 to 2,288 cm3, showing excellent agreement among all readers in 87% of cases (52/60) with a difference of less than 10% or less than 10 cm3 In 70% of the cases, TMTV4 equaled TMTV1, requiring no additional reader interaction. Differences in the TMTV4 were exclusively related to reader interpretation of lesion inclusion or physiologic high-uptake region removal, not to the choice of software. For 5 cases, large TMTV differences (>25%) were due to disagreement about inclusion of diffuse splenic uptake. Conclusion: The proposed segmentation method enabled highly reproducible TMTV measurements, with minimal reader interaction in 70% of the patients. The inclusion or exclusion of diffuse splenic uptake requires definition of specific criteria according to lymphoma subtype. The publicly available proposed benchmark allows comparison of study results and could serve as a reference to test improvements using other segmentation approaches.

18F-DCFPyL PSMA PET/CT Tracheobronchial Uptake in Patients with Prostate Cancer: Incidence and Etiology.

We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.

A 18F-FDG PET/CT based radiomics nomogram for predicting disease-free survival in stage II/III colorectal adenocarcinoma.

OBJECTIVES: This study aimed to establish a clinical nomogram model based on a radiomics signatures derived from 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET/CT) and clinical parameters to predict disease-free survival (DFS) in patients with stage II/III colorectal adenocarcinoma. Understanding and predicting DFS in these patients is key to optimizing treatment strategies. METHODS: A retrospective analysis included 332 cases from July 2011 to July 2021 at The Sixth Affiliated Hospital, Sun Yat-sen University, with PET/CT assessing radiomics features and clinicopathological features. Univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox, and multivariable Cox regression identified recurrence-related radiomics features. We used a weighted radiomics score (Rad-score) and independent risk factors to construct a nomogram. Evaluation involved time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: The nomogram, incorporating Rad-score, pN, and pT demonstrated robust predictive ability for DFS in stage II/III colorectal adenocarcinoma. Training cohort areas under the curve (AUCs) were 0.78, 0.80, and 0.86 at 1, 2, and 3 years, respectively, and validation cohort AUCs were 0.79, 0.75, and 0.73. DCA and calibration curves affirmed the nomogram's clinical relevance. CONCLUSION: The 18F-FDG PET/CT based radiomics nomogram, including Rad-score, pN, and pT, effectively predicted tumor recurrence in stage II/III colorectal adenocarcinoma, significantly enhancing prognostic stratification. Our findings highlight the potential of this nomogram as a guide for clinical decision making to improve patient outcomes.

Comparing the diagnostic performance of [18F]FDG PET/CT and [18F]FDG PET/MRI for detecting cardiac sarcoidosis: A meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]FDG PET/CT and [18F]FDG PET/MRI in detecting cardiac sarcoidosis. METHODS: An extensive search was conducted in the PubMed and Embase databases to identify available publications up to November 2023. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET/CT and [18F]FDG PET/MRI in patients with cardiac sarcoidosis. Sensitivity and specificity were evaluated using the DerSimonian and Laird method, with subsequent transformation via the Freeman-Tukey double inverse sine transformation. Publication bias was assessed using funnel plots and Egger's test. RESULTS: 16 articles involving 1361 patients were included in the meta-analysis. The overall sensitivity of [18F]FDG PET/CT in detecting cardiac sarcoidosis was 0.77(95%CI: 0.62-0.89), while the overall sensitivity of [18F]FDG PET/MRI was 0.94(95%CI: 0.84-1.00). The result indicated that [18F]FDG PET/MRI appears to a higher sensitivity in comparison to [18F]FDG PET/CT(P = 0.02). In contrast, the overall specificity of [18F]FDG PET/CT in detecting cardiac sarcoidosis was 0.90(95%CI: 0.85-0.94), while the overall specificity of [18F]FDG PET/MRI was 0.79(95%CI: 0.53-0.96), with no significant difference in specificity (P = 0.32). CONCLUSIONS: Our meta-analysis indicates that [18F]FDG PET/MRI demonstrates superior sensitivity and comparable specificity to [18F]FDG PET/CT in detecting cardiac sarcoidosis. However, the small number of PET/MRI studies limited the evidence of current results. To validate these results, larger, prospective studies employing a head-to-head design are needed.

The Role of FAPI PET Imaging in Pancreatic Cancer: A Meta-analysis Compared with 18F-FDG PET.

PURPOSE: Fibroblast activating protein is a promising target for tumor molecular imaging and therapy. Studies showed that fibroblast activating protein inhibitor (FAPI) radioactive tracers presented superiority over 18F-FDG PET/CT in the evaluation of various cancer types, including pancreatic cancer (PC). Therefore, we conducted this meta-analysis to evaluate and analyze the differences between 68Ga/18F-FAPI and 18F-FDG in PC, in order to provide evidence for the clinical application of FAPI PET imaging. METHODS: In the current meta-analysis, original studies published as of January 1, 2024 were analyzed using radiolabeled FAPI as a diagnostic radioactive tracer and compared to 18F-FDG for PET in PC. Databases searched included pubmed and web of science, and subject headings searched included PC and FAPI. The quality of the enrolled studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies 2, and the meta-analysis was conducted using R language. RESULTS: A total of seven studies including 322 patients compared the diagnostic performance of FAPI PET imaging and 18F-FDG PET/CT in PC. Overall, FAPI PET imaging showed higher pooled sensitivity (0.99 [95% CI: 0.97-1.00] vs. 0.84 [95% CI: 0.70-0.92]) and area under the curve (0.99 [95% CI: 0.98-1.00] vs. 0.91 [95% CI: 0.88-0.93]) than 18F-FDG PET/CT. The evidence showed that FAPI PET imaging is superior to 18F-FDG in pooled sensitivity to primary tumor, lymph node metastasis, and distant metastasis. Moreover, FAPI PET imaging improved TNM staging in 25% of PC patients and changed clinical management in 11.7% of PC patients compared to 18F-FDG. CONCLUSION: FAPI PET imaging is superior to that of 18F-FDG in the detection of primary PC, nodal and distant metastases, TNM staging and clinical management.

Clinical Performance Comparison of a Long Versus a Short Axial Field-of-View PET/CT Using EARL-Compliant Reconstructions.

PURPOSE: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision. PROCEDURES: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[18F]fluoro-D-glucose injection and underwent routine clinical ( ∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test. RESULTS: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra. CONCLUSION: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations.

Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy.

Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumor-selective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [18F]FDG (2-[18F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide 18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note, an OxaliPt(IV) linker is designed to construct an [18F]FDG-activated antibody-drug conjugate (Pt-ADC). Sequential injection of Pt-ADC and [18F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation, and we find that [18F]FDG is capable of deprotecting various radiotherapy-removable protecting groups (RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.

sICAM-1 concentrations are associated with inflammation in contralateral carotid plaque in patients with ischemic stroke.

BACKGROUND: Atherosclerotic plaques in the internal carotid artery are responsible for more than 15% of ischemic strokes. Carotid 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) detects plaque inflammation. Plasma ICAM-1 and LRP1 concentrations have been associated with inflammation in ipsilateral carotid plaque. The aim of the present study was to test the association between the soluble (s) form of these biomarkers and contralateral carotid plaques. METHODS: Prospective study conducted in 53 patients with a recent ischemic stroke and at least one atherosclerotic plaque in both carotid arteries. All of the patients underwent an early carotid 18F-FDG PET, and a blood sample was obtained at 7±1 days. Several plasma inflammatory markers were evaluated by Multiplex and sLRP1 levels were measured by commercial ELISA. Bivariate and multivariable linear regression was used to assess the association between inflammatory markers and the clinical variables, including contralateral maximum standardized uptake value (SUVmax) and mean SUVmax (mean of contralateral and ipsilateral SUVmax) of 18F-FDG uptake. Hazard ratio (HR) was estimated with Cox models adjusted for potential confounding factors to evaluate recurrence. RESULTS: Multivariable linear regression analysis showed an independent association between sICAM-1 and sVCAM-1 and mean SUVmax (CI=-0.064-0.325, p=0.004; CI=0.079-0.554, p=0.010). In addition, in bivariate regression analysis, sICAM-1 was associated with contralateral SUVmax (CI=0.049-0.382, p=0.012). Cox regression showed that mean SUVmax was associated with stroke recurrence (HR=5.604, p=0.044). CONCLUSIONS: sICAM-1 was independently associated with mean carotid plaque inflammation and with inflammation in contralateral plaque. sICAM-1 could be an indicator of plaque inflammation even in asymptomatic plaques.

Breast Cancer Subtype Prediction Model Employing Artificial Neural Network and 18F-Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography.

Introduction: Although positron emission tomography/computed tomography (PET/CT) is a common tool for measuring breast cancer (BC), subtypes are not automatically classified by it. Therefore, the purpose of this research is to use an artificial neural network (ANN) to evaluate the clinical subtypes of BC based on the value of the tumor marker. Materials and Methods: In our nuclear medical facility, 122 BC patients (training and testing) had 18F-fluoro-D-glucose (18F-FDG) PET/CT to identify the various subtypes of the disease. 18F-FDG-18 injections were administered to the patients before the scanning process. We carried out the scan according to protocol. Based on the tumor marker value, the ANN's output layer uses the Softmax function with cross-entropy loss to detect different subtypes of BC. Results: With an accuracy of 95.77%, the result illustrates the ANN model for K-fold cross-validation. The mean values of specificity and sensitivity were 0.955 and 0.958, respectively. The area under the curve on average was 0.985. Conclusion: Subtypes of BC may be categorized using the suggested approach. The PET/CT may be updated to diagnose BC subtypes using the appropriate tumor maker value when the suggested model is clinically implemented.

Case report: Evaluation of cutaneous squamous cell carcinoma metastasized to lymph nodes using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in a dog.

Introduction: 18F-fluorodeoxy-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is used with high sensitivity in human medicine for initial staging and treatment planning of cutaneous squamous cell carcinoma (SCC). To the best of our knowledge, 18F-FDG PET/computed tomography (CT) has not been used for canine cutaneous SCC with lymph node metastasis. Case presentation: A 13 year-old spayed female Maltese had rapidly growing flank SCC, which had previously recurred twice. Radiography revealed no metastases. On PET/CT imaging, increased FDG uptake was observed not only in the flank but also in the left axillary lymph node and left inguinal lymph node (standardized uptake value max [SUVmax]: 8.602, 5.354, and 1.96, respectively). Despite the evidence of metastasis, palliative skin mass resection with a 3-cm margin and lymph node dissection were performed. Histopathological examination confirmed the presence of metastases in both lymph nodes. Discussion: 18F-FDG PET/CT is valuable for the detection of metastatic tumors in various organs. Cutaneous SCC can accumulate 18F-FDG, making it detectable on PET/CT. In this dog with flank SCC, 18F-FDG-PET/CT showed high SUVmax values, indicating its potential for tumor assessment. In veterinary medicine, SUVmax values of 2.5-3.5 are commonly used to identify metastatic lymph nodes in other cancers. Therefore, the interpretation of an SUVmax of 1.96 in an inguinal lymph node for metastatic involvement may be uncertain. Owing to the partial volume effect, 18F-FDG PET/CT has limited sensitivity in identifying LN metastases, particularly in cases of small lesions. Lower SUVmax values adjusted for smaller sizes may better distinguish between benign and malignant lymph nodes. Hence, combining differentiated SUVmax cut-offs based on lymph node size with CT assessment could enhance lymph node evaluation and assist in surgical planning.

Radiomics based on 18F-FDG PET/CT for prediction of pathological complete response to neoadjuvant therapy in non-small cell lung cancer.

Purpose: This study aimed to establish and evaluate the value of integrated models involving 18F-FDG PET/CT-based radiomics and clinicopathological information in the prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) for non-small cell lung cancer (NSCLC). Methods: A total of 106 eligible NSCLC patients were included in the study. After volume of interest (VOI) segmentation, 2,016 PET-based and 2,016 CT-based radiomic features were extracted. To select an optimal machine learning model, a total of 25 models were constructed based on five sets of machine learning classifiers combined with five sets of predictive feature resources, including PET-based alone radiomics, CT-based alone radiomics, PET/CT-based radiomics, clinicopathological features, and PET/CT-based radiomics integrated with clinicopathological features. Area under the curves (AUCs) of receiver operator characteristic (ROC) curves were used as the main outcome to assess the model performance. Results: The hybrid PET/CT-derived radiomic model outperformed PET-alone and CT-alone radiomic models in the prediction of pCR to NAT. Moreover, addition of clinicopathological information further enhanced the predictive performance of PET/CT-derived radiomic model. Ultimately, the support vector machine (SVM)-based PET/CT radiomics combined clinicopathological information presented an optimal predictive efficacy with an AUC of 0.925 (95% CI 0.869-0.981) in the training cohort and an AUC of 0.863 (95% CI 0.740-0.985) in the test cohort. The developed nomogram involving radiomics and pathological type was suggested as a convenient tool to enable clinical application. Conclusions: The 18F-FDG PET/CT-based SVM radiomics integrated with clinicopathological information was an optimal model to non-invasively predict pCR to NAC for NSCLC.

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5. CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

18F-Fluorodeoxyglucose (18F-FDG) PET/CT Appearance of Baastrup's Disease and Its Multimodality Correlation.

Baastrup's disease (BD), commonly known as "kissing spine syndrome," presents a significant cause of lower back pain, predominantly affecting the lumbar region. Diagnosis is often challenging due to its symptomatology and radiographic presentation. Herein, we present a case series demonstrating the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in diagnosing BD accurately, particularly in oncologic settings where it may mimic metastatic lesions. Through a series of cases, we demonstrate the distinctive imaging features of BD on 18F-FDG PET/CT and its differentiation from malignancies. In addition, we emphasize the importance of clinical awareness and proper correlation with CT or MRI to avoid misinterpretation. Furthermore, we discuss the pathophysiology, clinical presentation, and diagnostic modalities of BD, highlighting its underdiagnosis and potential to mimic metastasis on imaging. By enhancing recognition of BD's appearance on 18F-FDG PET/CT, this study aims to prevent misdiagnoses, reduce unnecessary investigations, and ultimately improve patient care in oncologic practice.

Measurement of hepatic glucose (18F-fluorodeoxyglucose) uptake with positron emission tomography-magnetic resonance imaging in fumonisin B intoxicated rabbit bucks.

Rabbit bucks (bodyweight 5 kg) underwent dietary intoxication with fumonisin B series mycotoxins (FB1 + FB2 + FB3, 15 mg/kg diet) for 14 days to test the applicability of positron emission tomography-magnetic resonance (PET MR) hybrid imaging in characterizing experimentally induced mild hepatotoxicosis. 18F-fluorodeoxyglucose (18F-FDG) radiotracer-aided imaging was performed before and after FBs administration on identical animals, and at both time points, blood was sampled for haematology and clinical chemistry. Kinetic PET image analysis revealed time-activity curves with uptake maxima below 1 min in the liver, renal cortex, portal vein, lung and coarctatio aortae. In the frame of static PET image analysis, based on the standardized uptake value (SUV), the so-called metabolic liver volume (MLV, liver volume defined by over 0.9 × average liver SUV) and the total liver glycolysis (TLG, MLV multiplied by the SUVmean) were calculated. Mycotoxicosis increased total liver glycolysis (p < 0.04) after 14 days and liver tissue TLG inhomogeneity was minimal. Pearson correlation between TLG and alkaline phosphatase (ALP) was positive (0.515), while negative with LDH and AST (- 0.721 and - 0.491, respectively). Results indicate a slight hepatic mycotoxin effect and significantly increased glucose uptake intensity, which has been sensitively detected with molecular imaging (18F-FDG PET MRI) in the rabbit model.

Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer.

About 75% of breast tumors show an overexpression of the estradiol receptor (ER), making it a valuable target for tumor diagnosis and therapy. To date, 16α-[18F]fluoroestradiol (FES) is the only FDA-approved imaging probe for the positron emission tomography (PET) imaging of ER-positive (ER+) breast cancer. However, FES has the drawback of a high retention in the liver. Therefore, the aim of this study was the development and preclinical evaluation of estradiol (E2) derivatives with different lipophilicity. Three 18F-labeled prosthetic groups (two glycosyl and one PEG azide) were chosen for conjugation with ethinyl estradiol (EE) by 18F-CuAAC (Cu-catalyzed azide-alkyne cycloaddition). The cellular uptake in ER+ MCF-7 tumor cells was highest for the less hydrophilic derivative (18F-TA-Glyco-EE). In nude mice bearing different breast tumors (ER+ MCF-7 and T47D versus ER- MDA-MB-231), 18F-TA-Glyco-EE revealed a high uptake in the liver (13%ID/g, 30 min p.i.), which decreased over 90 min to 1.2%ID/g, indicating fast hepatobiliary clearance. The statistically significant difference of 18F-TA-Glyco-EE uptake in T47D compared to MDA-MB-231 tumors at 60-90 min p.i. indicated ER-specific uptake, whereas in vivo PET imaging did not provide evidence for specific uptake of 18F-TA-Glyco-EE in MCF-7 tumors, probably due to ER occupation by E2 after E2-dependent MCF-7 tumor growth in mice. However, in vitro autoradiography revealed a high specific binding of 18F-TA-Glyco-EE to ER+ tumor slices. We conclude that 18F-TA-Glyco-EE, with its increased hydrophilicity after deacetylation in the blood and thus rapid washout from non-target tissues, may be a viable alternative to FES for the PET imaging of breast cancer.

Augmenting CT-Guided Bone Biopsies Using 18F-FDG PET/CT Guidance.

Computer tomography (CT)-guided percutaneous core biopsies are currently the gold standard in diagnostic procedures for patients with bone lesions of unknown kind. CT-guided biopsies can lead to misdiagnosis or repetition of biopsies in case of small or heterogeneous lesions. We hypothesize that molecular image guidance could be used to optimize the biopsy strategy, by supporting the detection of heterogeneous lesions or lesions without radiographic substrate. To evaluate this hypothesis, we investigated if and how the addition of 2-deoxy-2-18F-fluoro-D-glucose-positron emission tomography (18F-FDG-PET)/CT could augment routine CT-guided bone biopsies. To this end, 106 patients who underwent a CT-guided bone biopsy between April 2019 and April 2020, obtained from either a vertebral or peripheral bone, were included. Patients were divided into 2 groups: 36 patients received an 18F-FDG-PET/CT scan prior to their CT-guided bone biopsy (PET group), while 70 patients only had a morphological CT scan (CT group). Histopathology was used to categorize biopsies into five subgroups (inconclusive, benign, malignant or infectious disease, or normal tissue). In the PET group, the number of conclusive biopsies was significantly higher compared to the CT group (N = 33/36 (92%) versus N = 53/70 (76%); p < 0.05). Furthermore, the number of first-try biopsies was lower in the PET group compared to the CT group (1.9 vs. 2.54, p = 0.051). In conclusion, 18F-FDG-PET/CT imaging significantly increased the success rate of first-try CT-guided bone biopsies by showing less inconclusive biopsies and misdiagnosis.

Predictive and Prognostic 18F-Fluorocholine PET/CT Radiomics Nomogram in Patients with Castration-Resistant Prostate Cancer with Bone Metastases Treated with 223Ra.

PURPOSE: We aimed to develop a nomogram able to predict treatment failure, skeletal events, and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). PATIENTS AND METHODS: Patients from the Castilla-La Mancha Spanish region were prospectively included in the ChoPET-Rad multicenter study from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using the Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. RESULTS: Median progression-free survival (PFS) and OS were 4 and 14 months (mo), respectively. The variables that showed independent and significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p = 0.022) and the characteristics of BM on the CT portion of PET/CT (p = 0.017). In the case of OS, the significant variables were therapeutic failure (p = 0.038), the number of lines received after 223Ra (p < 0.001), average SUVmax (p = 0.002), bone marrow infiltration in FCH PET/CT (p = 0.006), and interim FCH PET/CT response (p = 0.048). Final nomograms included these variables, showing good discrimination among the 100 patients included in our study. In the study of skeletal events, only OS showed a significant association in the multivariate analysis, resulting in an inconsistent nomogram design. CONCLUSIONS: FCH PET/CT appears to be a good tool for evaluating patients eligible for treatment with 223Ra, as well as for their follow-up. Thus, findings derived from it, such as the morphological characteristics of BM in the CT, bone marrow infiltration, or the response to 223Ra in the interim study, have proven to be solid and useful variables in the creation of nomograms for predicting therapeutic failure and OS.

The Prognostic Significance of Pontine-White Matter Score in Primary Central Nervous System Lymphoma Patients.

BACKGROUND: Limited data exist on the significance of PET imaging and quantitative PET parameters in primary central nervous system (CNS) lymphoma due to its relative rarity. This study was conducted to investigate the prognostic value of a novel internal standardization indicator, the pontine-white matter (PW) score, in primary CNS lymphoma patients undergoing post-treatment 18F-FDG PET/CT and PET/MR imaging. METHODS: From January 2014 to December 2022, eligible patients with primary CNS lymphoma who underwent post-treatment PET imaging were enrolled. Using the FDG uptake of the pons and white matter as an internal reference, the PW score was graded based on the metabolism of the post-therapeutic lesion for each patient, and its associations with patients' prognosis were investigated. RESULTS: In total, 41 patients with post-treatment PET/CT and 49 patients with post-treatment PET/MR imaging were enrolled. ROC curve analysis indicated that the PW score possessed robust discriminative ability in distinguishing patients with worse outcomes. Furthermore, a higher PW score was significantly correlated with and identified as an independent prognostic indicator for, worse prognosis in both the PET/CT and PET/MR cohorts. CONCLUSION: The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes.

Elevated cerebral blood flow proxy with increased beta-amyloid burden in Alzheimer's disease preclinical phase evaluated by dual-phase 18F-florbetaben positron emission tomography.

This study investigated the earliest change of cerebral blood flow (CBF) and its relationship with ß-amyloid (Aß) burden in preclinical Alzheimer's disease (AD) employing dual-phase 18F-florbetaben (FBB) PET. Seventy-one cognitively normal (NC) individuals were classified as Aß negative (Aß-NC) or positive (Aß+NC) based on two different cutoff values: an SUVR of > 1.08 and a Centiloid scale of > 20. The PET scans were acquired in two phases: an early phase (0-10 min, eFBB) and a delayed phase (90-110 min, dFBB), which were averaged to generate single-frame images for each phase. Furthermore, an R1 parametric map was generated from the early phase data using a simplified reference tissue model. We conducted regional and voxel-based analyses to compare the eFBB, dFBB, and R1 images between the Aß positive and negative groups. In addition, the correlations between the CBF proxy R1 and the dFBB SUVR were analyzed. The Aß+NC group showed significantly higher dFBB SUVR in both the global cerebral cortex and target regions compared to the Aß-NC group, while no significant differences were observed in eFBB SUVR between the two groups. Furthermore, the Aß+NC group exhibited significantly higher R1 values, a proxy for cerebral perfusion, in both the global cerebral cortex and target regions compared to the Aß-NC group. Significant positive correlations were observed between R1 and dFBB SUVR in both the global cerebral cortex and target regions, which remained significant after controlling for demographics and cognitive profiles, except for the medial temporal and occipital cortices. The findings reveal increased CBF in preclinical AD and a positive correlation between CBF and amyloid pathology. The positive correlation between R1 and amyloid burden may indicate a compensatory mechanism in the preclinical stage of Alzheimer's disease, but to elucidate this hypothesis, further longitudinal observational studies are necessary.

The impact of introducing deep learning based [18F]FDG PET denoising on EORTC and PERCIST therapeutic response assessments in digital PET/CT.

BACKGROUND: [18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up. RESULTS: 110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients. CONCLUSIONS: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.