PET Parameters Research Articles

Prognostic value of interim [68Ga]Ga-DOTA-TOC PET/CT in patients with neuroendocrine tumour who underwent peptide receptor radionuclide therapy.

This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT). Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan-Meier analysis, log-rank tests, and a Cox proportional-hazards regression model. Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32-74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ -10%, hazard ratio [HR] = 3.053 [1.003-9.289], p = 0.049) and high ∆TRE (≥ -21%, HR = 3.567 [1.144-11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055-10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194-12.695], p = 0.024) were significant predictors of shorter PFS. The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT. Question Peptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established. Findings Progression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT. Clinical relevance Interim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.

A New Tool for Extracting Static and Dynamic Parameters from [18F]F-DOPA PET/CT in Pediatric Gliomas

Background/Objectives: PET imaging with [18F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. Methods: In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [18F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [18F]F-DOPA uptake. A total of 73 subjects with treatment-naïve low- and high-grade gliomas, who underwent brain MRI within two weeks of [18F]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. Results: For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357); however, significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Conclusions: Our framework aids in analyzing [18F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

PET/CT imaging of differentiated and medullary thyroid carcinoma using the novel SSTR-targeting peptide [18F]SiTATE - first clinical experiences.

The novel 18F-labeled somatostatin receptor (SSTR)-directed radiotracer [18F]SiTATE demonstrated promising results for the imaging of various SSTR-expressing tumor types. Although thyroid carcinomas (TC) express SSTR, data on [18F]SiTATE PET/CT imaging in TC are lacking. This study explores the use of [18F]SiTATE PET/CT in a patient cohort with histologically proven TC. As part of a prospective observational study at a single tertiary cancer center, 21 patients with TC (10 medullary (MTC) and 11 differentiated (DTC)) who underwent at least one [18F]SiTATE PET/CT were included (37 scans in total). Mean SUVmax and SUVmean of tumoral lesions, mean total-tumor-volume (TTV), and whole-body (WB)-SUVmax and WB-SUVmean on PET with their standard deviations (SDs) were determined. PET parameters were correlated to clinical parameters including tumor marker levels (thyroglobulin for DTC, calcitonin for MTC). 89 lesions were included in the analysis. Metastases were localized in the bone, lymph nodes, lung, soft tissue, and thyroid bed. Osseous (31 lesions; SUVmax 8.6 ± 8.0; SUVmean 5.8 ± 5.4) and nodal (37 lesions; SUVmax 8.7 ± 7.8; SUVmean 5.7 ± 5.4) metastases showed the highest uptake. The MTC disease burden on PET significantly correlated with the calcitonin tumor marker level (e.g., TTV: r = 0.771, r2 = 0.594, p = 0.002). For DTC, no such correlation was present. Our data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.

Combination of FDG PET/CT radiomics and clinical parameters for outcome prediction in patients with non-Hodgkin's lymphoma.

The purposes was to build model incorporating PET + computed tomography (CT) radiomics features from baseline PET/CT + clinical parameters to predict outcomes in patients with non-Hodgkin lymphomas. Cohort of 138 patients with complete clinical parameters and follow up times of 25.3 months recorded. Textural analysis of PET and manual correlating contouring in CT images analyzed using LIFE X software. Defined outcomes were overall survival (OS), disease free-survival, radiotherapy, and unfavorable response (defined as disease progression) assessed by end of therapy PET/CT or contrast CT. Univariable and multivariable analysis performed to assess association between PET, CT, and clinical. Male (P = 0.030), abnormal lymphocytes (P = 0.030), lower value of PET entropy (P = 0.030), higher value of SHAPE sphericity (P = 0.002) were significantly associated with worse OS. Advanced stage (III or IV, P = 0.013), abnormal lymphocytes (P = 0.032), higher value of CT gray-level run length matrix (GLRLM) LRLGE mean (P = 0.010), higher value of PET gray-level co-occurrence matrix energy angular second moment (P < 0.001), and neighborhood gray-level different matrix (NGLDM) busyness mean (P < 0.001) were significant predictors of shorter DFS. Abnormal lymphocyte (P = 0.033), lower value of CT NGLDM coarseness (P = 0.082), and higher value of PET GLRLM gray-level nonuniformity zone mean (P = 0.040) were significant predictors of unfavorable response to chemotherapy. Area under the curve for the three models (clinical alone, clinical + PET parameters, and clinical + PET + CT parameters) were 0.626, 0.716, and 0.759, respectively.

Maximum standardized uptake value-to-tumor size ratio in fluorodeoxyglucose F18 positron emission tomography/computed tomography: a simple prognostic parameter for non-small cell lung cancer.

By correcting the effect of tumor size on metabolic activity, the maximum standardized uptake value-to-tumor size (SUVmax:tumor size) ratio on fluorodeoxyglucose F18 positron emission tomography (18F-FDG PET)/computed tomography (CT) scans can be a prognostic parameter of non-small cell lung cancer (NSCLC). The current study evaluates the prognostic value of SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans in patients with NSCLC. Furthermore, the SUVmax:tumor size ratio is compared with other established PET parameters. This study included 108 patients with NSCLC who underwent pretreatment 18F-FDG PET/CT scans and curative lung surgery. The associations between the SUVmax:tumor size ratio and other conventional PET parameters were investigated. The recurrence-free survival according to the SUVmax:tumor size ratio was also analyzed. In addition, the SUVmax:tumor size ratio was compared according to postoperative pathologic findings. In total, 72 (66.7%) of the 108 participants presented with adenocarcinoma (ADC). Nineteen (17.6%) patients experienced recurrence during a median follow-up period of 32.3 months. The median SUV max:tumor size ratio was 2.37 (1.23 for ADCs and 3.90 for other histologic types). The SUVmax:tumor size ratio was associated with SUVmax and mean SUV, as well as metabolic tumor volume and total lesion glycolysis. Patients with an SUVmax:tumor size ratio higher than the median had a worse recurrence outcome than those with an SUVmax:tumor size ratio lower than the median. Participants with ADC who presented with lymphovascular invasion had a higher SUVmax:tumor size ratio than those without. The presence of lymph node metastasis and advanced histologic grade were associated with a high SUVmax:tumor size ratio in patients with ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans was associated with aggressive tumor behavior and poor outcome in NSCLCs, particularly ADC. The SUVmax:tumor size ratio on pretreatment 18F-FDG PET/CT scans has a prognostic value in patients with NSCLCs, especially ADC.

Establishing a predictive model for tumor mutation burden status based on 18F-FDG PET/CT and clinical features of non-small cell lung cancer patients.

Tumor mutation burden (TMB) has emerged as a promising biomarker for immune checkpoint inhibitors (ICI) response, but its detection through whole exome sequencing (WES) is costly and invasive. This study aims to establish a predictive model for TMB using baseline metabolic parameters (MPs) of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) and clinical features in non-small cell lung cancer (NSCLC) patients, potentially offering a non-invasive and cost-effective method to predict TMB status. A total of 223 NSCLC patients with baseline 18F-FDG PET/CT scans and TMB detection results were retrospectively enrolled from January 2019 to September 2023, and were divided into two groups: TMB-high (≥4 mutations/Mb, 96 patients) and TMB-low (<4 mutations/Mb, 127 patients). Twelve clinical features and five PET parameters were assessed. Univariate analysis was conducted in all patients to reveal the preliminary associations between variables and TMB status. All patients were randomly divided into a training set (n=135) and a validation set (n=88). Feature selection was performed using lasso regression and logistic regression analyses. A predictive model and nomogram were established with the features selected above. Decision curve analysis (DCA) was performed to assess the clinical utility of the developed model. Two clinical features and two PET parameters were identified through lasso regression and logistic regression analysis including pathology type, cancer antigen 125 (CA125) level, maximum standardized uptake value (SUVmax), and metabolic tumor volume (MTV). The predictive model exhibited an area under the curve (AUC) of 0.822 [95% confidence interval (CI), 0.751-0.894], and internal validation yielded an AUC of 0.822 (95% CI, 0.731-0.912). The model was well-calibrated. The developed nomogram, incorporating the four selected variables, showed promising potential in evaluating TMB status in NSCLC patients. In this study, a predictive model combining 18F-FDG PET/CT and clinical features of NSCLC patients effectively distinguished between TMB-high and TMB-low status. The nomogram generated from this model holds significant promise for predicting TMB status, offering valuable insights for clinical decision-making.

18F]AlF-NOTA-FAPI-04 PET/CT for Predicting Pathologic Response of Resectable Esophageal Squamous Cell Carcinoma to Neoadjuvant Camrelizumab and Chemotherapy: A Phase II Clinical Trial.

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of 18F-labeled fibroblast activation protein inhibitor ([18F]AlF-NOTA-FAPI-04, denoted as 18F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent 18F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On 18F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUVmax (area under the curve [AUC], 0.87; P = 0.0026), SUVpeak (AUC, 0.89; P = 0.0017), SUVmean (AUC, 0.88; P = 0.0021), TBRmax (AUC, 0.86; P = 0.0031), and TBRmean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%-81.82% and specificities of 83.33%-100%. Changes in SUVmax (AUC, 0.81; P = 0.0116), SUVpeak (AUC, 0.82; P = 0.0097), SUVmean (AUC, 0.81; P = 0.0116), and TBRmean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: 18F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.

Comparison of PSMA immunohistochemistry scoring systems to parametric [18F]PSMA-1007 PET/MRI in primary prostate cancer.

Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. Primary intermediate- and high-risk prostate cancer patients received an [18F]PSMA-1007 PET/MRI followed by radical prostatectomy. SUVmax, SUVmean and Ki of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity scorepredominant intensity (IRSpredominant intensity), IRS classificationpredominant intensity, IRSmean intensity, IRS classificationmean intensity, Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman's rank correlation coefficients (ρ) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUVmax (ρ 0.615 p < 0.0001) and SUVmean (ρ 0.570, p < 0.0001) and the second best correlation with Ki (ρ 0.411, p = 0.0030). SDI had the best correlation with Ki (ρ -0.440, p = 0.0014) and the second best correlation with SUVmax (ρ -0.516, p = 0.0001) and SUVmean (ρ -0.490, p = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95% CI 0.495-0.797) and SDI (ICC 0.546, 95% CI 0.354-0.725). H-score had the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system.

Predictive Value of Quantitative Parameters of 18F-FDG PET/CT in Patients with Liposarcoma.

The purpose of this study was to evaluate the predictive features of baseline F-18-fluorodeoxy-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT) parameters in patients with dedifferentiated liposarcomas (DDLPSs) and well-differentiated liposarcomas (WDLPSs) receiving systemic treatment. A total of 24 patients with liposarcoma who underwent longitudinal 18F-FDG PET/CT in systemic therapy were included. All volumetric segmentation of each tumor section and semiquantitative imaging parameters were extracted from the axial field of view from both PET and CT images. Maximum, mean, and minimum standardized uptake values (SUVmax, SUVmean, and SUVmin), Hounsfield units (HUs), and their respective changes from baseline and posttreatment were calculated. The voxel values from unenhanced CT images were correlated with PET-derived parameters. The 18F-FDG uptake decreased by more than 56% on average in responders for both SUVmax and SUVmean in DDLPS. There was a decrease in HUmax in DDLPS among responders. Using AUC > 0.8 as a reasonable predictor, we found that the ratios of SUVmaxD/HUmean, SUVmaxD/HUmedian, and SUVmeanD/HUmedian at baseline were significant indicators of the response to treatment in patients with liposarcoma. The changes in SUVmean and not just SUVmax parameters could be considered as accurate tumor response indicators. For the first time, we introduced baseline SUV/HU ratios as a valuable diagnostic tool in predicting liposarcoma treatment outcomes. This ability was not revealed by classic semiquantitative PET or CT parameters at baseline.

Baseline 18F-FDG PET Radiomics Predicting Therapeutic Efficacy of Diffuse Large B-Cell Lymphoma after R-CHOP (-Like) Therapy.

Objective: This study aimed to predict therapeutic efficacy among diffuse large B-cell lymphoma (DLBCL) after R-CHOP (-like) therapy using baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) radiomics. Methods: A total of 239 patients with DLBCL were enrolled in this study, with 82 patients having refractory/relapsed disease. The radiomics signatures were developed using a stacking ensemble approach. The efficacy of the radiomics signatures, the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), conventional PET parameters model, and their combinations in assessing refractory/relapse risk were evaluated using receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and decision curve analysis. Results: The stacking model, along with the integrated model that combines stacking with the NCCN-IPI and SDmax (the distance between the two lesions farthest apart, normalized to the patient's body surface area), showed remarkable predictive capabilities with a high area under the curve (AUC), sensitivity, specificity, PPV, NPV, accuracy, and significant net benefit of the AUC (NB-AUC). Although no significant differences were observed between the combined and stacking models in terms of the AUC in either the training cohort (AUC: 0.992 vs. 0.985, p = 0.139) or the testing cohort (AUC: 0.768 vs. 0.781, p = 0.668), the integrated model exhibited higher values for sensitivity, PPV, NPV, accuracy, and NB-AUC than the stacking model. Conclusion: Baseline PET radiomics could predict therapeutic efficacy in DLBCL after R-CHOP (-like) therapy, with improved predictive performance when incorporating clinical features and SDmax.

PSMA PET improves characterization of dural-based intracranial lesions in patients with metastatic prostate cancer

PurposeTheranostic approaches combining prostate-specific membrane antigen (PSMA)-PET/CT or PET/MRI with PSMA-targeted radionuclide therapy have improved clinical outcomes in patients with prostate cancer (PCa) especially metastatic castrate resistant prostate cancer. Dural metastases in PCa are rare but can pose a diagnostic challenge, as meningiomas, a more common dural based lesions have been shown to express PSMA. The aim of this study is to compare PSMA PET parameters between brain lesions classified as dural metastases and meningiomas in prostate cancer patients. MethodsA retrospective analysis of PSMA PET/CT scans in patients with PCa and intracranial lesions was conducted. Brain lesions were categorized as dural metastases or meningiomas based on MRI characteristics, longitudinal follow-up, and histopathological characteristics. Standardized uptake values (SUVmax) of each brain lesion were measured, along with SUV ratio referencing parotid gland (SUVR). SUVs between lesions classified as metastases and meningiomas, respectively, were compared using Mann-Whitney-test. Diagnostic accuracy was evaluated using ROC analysis. Results26 male patients (median age: 76.5 years, range: 59–96 years) met inclusion criteria. A total of 44 lesions (7 meningiomas and 37 metastases) were analyzed. Median SUVmax and SUVR were significantly lower in meningiomas compared to metastases (SUVmax: 2.7 vs. 11.5, p = 0.001; SUVR: 0.26 vs. 1.05, p < 0.001). ROC analysis demonstrated AUC 0.903; the optimal cut-off value for SUVR was 0.81 with 81.1 % sensitivity and 100 % specificity. ConclusionPSMA PET has the potential to differentiate meningiomas from dural-based metastases in patients with PCa, which can optimize clinical management and thus improve patient outcomes.

The Value of PSMA-RADS Version 2.0 in the Assessment of Pulmonary Metastases in Patients With Prostate Cancer and the Improvement of Differential Diagnosis Efficiency by PSMA PET/CT Parameters.

The aim of this study was to investigate the application of PSMA-RADS version 2.0 in assessment of pulmonary metastases in patients with prostate cancer and whether PSMA PET/CT parameters provide incremental value. From October 2016 to July 2023, PC patients with pulmonary opacities (including pulmonary metastases, lung cancer, and pulmonary benign opacities) who underwent Al18F-PSMA-BCH PET/CT scans were retrospectively analyzed. CT imaging characteristics, including the longest diameter, density, smoothness, lobulation, pleural retraction, and vacuole sign, as well as PET parameters including SUVmax and tumor-to-background ratio, were measured and analyzed. Additionally, the pulmonary PSMA-RADS score for each patient was determined. Independent predictors of pulmonary metastases were identified through univariate analysis and multivariate logistic regression analysis, which were utilized to construct a parallel diagnostic test. The differential diagnostic performances were evaluated using receiver operating characteristic analysis. A total of 148 pulmonary opacities from 96 patients were retrospectively included. The number of pulmonary benign opacities, lung cancer, and pulmonary metastases were 48 (32.4%), 20 (13.5%), and 80 (54.1%), respectively. The number of opacities across different PSMA-RADS scores from 2 to 5 was 8 (5.4%), 88 (59.5%), 7 (4.7%), and 45 (30.4%). SUVmax and smooth edges were independent predictors of pulmonary metastases (both P < 0.05), and the AUC of the parallel test for these 2 parameters was 0.86 (95% confidence interval: 0.79, 0.94; P < 0.001). Furthermore, the diagnostic accuracy of the parallel test across PSMA-RADS score from 2 to 5 was 85.7%, 79.6%, 100%, and 92.9%, respectively. Al18F-PSMA-BCH PET/CT parameters were helpful in differentiating pulmonary metastases in PC patients and provided incremental value when integrated with PSMA-RADS version 2.0.

Significance of incidental thyroid 18 F-fluorocholine uptake in patients with hyperparathyroidism imaged for localizing hyperfunctioning parathyroid glands.

18 F-fluorocholine PET/CT is considered the imaging gold standard for detection of hyperfunctioning parathyroid glands . However, increased uptake might also occur in the thyroid gland. The aim of our study was to assess the incidence and significance of 18 F-fluorocholine uptake in the thyroid gland in patients with hyperparathyroidism. This retrospective study includes 195 consecutive patients with hyperparathyroidism, who underwent 18 F-fluorocholine PET/CT, for detection of hyperfunctioning parathyroid glands. PET/CT images were reviewed by two nuclear medicine physicians for the presence of focal or diffuse thyroid uptake. PET/CT results were compared with laboratory parameters, ultrasonography, EU-TIRADS classification in the presence of thyroid nodules, cytology, and final histology. 25 patients (13%) showed 18 F-fluorocholine uptake in the thyroid gland: focal thyroid uptake (FTU) in 7 patients (4%), diffuse thyroid uptake (DTU) in 8 patients (4%), and combined uptake (FTU + DTU) in 10 patients (5%), with a total of 20 active thyroid nodules. There was no correlation between EU-TIRADS classification and PET parameters. One highly 18 F-fluorocholine active thyroid nodule and one isoactive thyroid nodule turned out to be papillary thyroid cancers in the final histology; 50% of the patients with DTU had Hashimoto's thyroiditis. Incidental 18 F-fluorocholine uptake in the thyroid gland was observed in 13% of patients. As reported for 18 F-FDG, focal 18 F-fluorocholine uptake might represent thyroid cancer and should be evaluated with ultrasound and, if indicated, with fine-needle aspiration cytology. Diffuse 18 F-fluorocholine uptake most likely represents multinodular goiter or Hashimoto's thyroiditis.

Quantitative 68Ga-PSMA-11 PET and Clinical Outcomes in Metastatic Castration-resistant Prostate Cancer Following 177Lu-PSMA-617 (VISION Trial).

Background Lutetium 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUVmean and SUVmax), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUVmean quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUVmean was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUVmean increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUVmean quartiles versus SOC only, with no identifiable optimum among participants receiving 177Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [P < .05] and 1.02-1.03 [P < .001], respectively) and OS (HR range, 1.36-2.12 [P < .006] and 1.04 [P < .001], respectively). Conclusion Baseline 68Ga-PSMA-11 PET/CT whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUVmean, with evidence for benefit at all SUVmean levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Primary tumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET/CT for the prediction of biochemical recurrence in prostate cancer

PurposeThe aim of this study is to research the value of the texture analysis of primary tumors in pre-treatment [68Ga]Ga-PSMA PET in the prediction of the development of biochemical recurrence (BCR) in prostate cancer patients who underwent definitive therapies. Methods51 patients with prostate adenocarcinoma who had a pre-treatment [68Ga]Ga-PSMA-11 PET/CT and underwent definitive radiotherapy (RT) or radical prostatectomy (RP) were included in the study. Demographics, clinicopathologic features, the presence of BCR, and the last follow-up date of patients were recorded. Textural and conventional PET parameters (maximum standardized uptake value (SUVmax), total lesion-PSMA (TL-PSMA), and PSMA-tumor volume (PSMA-TV)) were obtained from PET/CT images using LifeX program. Parameters were grouped using the Youden index in ROC analysis. Factors predicting the BCR were determined using Cox regression analyses. Results29 (56.9%) patients have received primary curative RT, while the remaining 22 (43.1%) patients have undergone RP. 5 (22.7%) patients with RP and 3 (10.3%) patients with curative RT have developed BCR during the follow-up. INTENSITY-BASED-minimum grey level (P=.050), GLCM-sum variance (P=.019), and GLCM-cluster prominence (P=.050) were associated with BCR in univariate analysis. INTENSITY-BASED-minimum grey level (P=.009) and GLCM-sum variance (P=.004) were found as independent predictors of BCR in the multivariate analysis. ConclusionTumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET is associated with a high risk of BCR in PCa patients who underwent definitive therapies.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [18F]FDG Imaging

PurposeLeft ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection.ProceduresSeventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard.ResultsNine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555–0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571–0.964), respectively.ConclusionsVolumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma with extranodal involvement.

The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

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

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. 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. 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. The study demonstrated that the PW score was an effective prognostic indicator for identifying post-treatment primary CNS lymphoma patients with worse outcomes.

Prognostic Importance of 18F-FDG Positron Emission Tomography in Uterine Cervical Cancer.

The aim of this study was to evaluate the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the uterine cervix cancer patients. Thirty-two women (mean age: 52.7±12.6) who underwent 18F-FDG PET/CT for staging of uterine cervix cancer were retrospectively recruited for the study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors, lymph nodes, and distant metastases were calculated from 18F-FDG PET/CT images using the 40% threshold. Patients were divided into groups according to the presence of pelvic and para-aortic lymph node involvement on 18F-FDG PET/CT images. Life tables and Kaplan-Meier analyses were performed to compare the mean survival times of the different groups. Primary tumor of 27 (84%) patients were 18F-FDG avid. The median SUVmax, SUVmean, MTV, and TLG of the primary tumors were 12.4, 6.1, 13.2 cm3 and 87.8 g/mL x cm3 respectively. Pathological uptake was detected in pelvic 14 (44%) patients and in paraaortic lymph nodes in 3 (10%) para-aortic lymph nodes. The median whole-body MTV and TLG were 21.7 cm3 and 91.1 g/mL x cm3. Disease progression was detected in 7 (22%) patients within a median follow-up period of 20.9 (minimum-maximum: 3-82) months. The only significant PET parameter to predict progression-free survival was SUVmax in the primary tumor (p=0.038). During follow-up period 8 patients died. SUVmax (p=0.007), MTV (p=0.036), TLG (p=0.001) of primary tumor, presence of pathological uptake on pelvic or paraaortic lymph nodes (p=0.015), whole-body MTV (p=0.047) and whole-body TLG (p=0.001) were found statistically significant PET parameters to predict overall survival. Metabolic parameters of primary tumors derived from 18F-FDG PET/CT images have prognostic importance for patients with uterine cervical carcinoma. In patients with metastatic disease, higher whole-body MTV and TLG are also associated with poor prognosis.