EJNMMI Research最新文献

Background: Over the past decade, numerous treatment options have emerged for patients with locally advanced and metastatic neuroendocrine tumours (NETs). Nevertheless, the optimal timing of treatment interventions remains uncertain, given the highly variable disease course observed in these patients, even when patients have the same tumour stage and grade. The aim of the study was to evaluate the predictive role of standardized uptake values (SUVs) and volumetric parameters obtained from pretreatment [68Ga]Ga-DOTA-TATE for response to SSA therapy in patients with NET. In this retrospective study, we included 42 patients (21 women, 21 men; age range: 46-84 years) with histologically confirmed, metastatic, NET (G1 13, G2 28 cases); median Ki-67 index 5%, range 1-16) who received long acting SSA as a first line treatment and underwent [68Ga]Ga-DOTA-TATE PET/CT before SSA treatment. For all [68Ga]Ga-DOTA-TATE avid lesion SUVmax, SUVmean, somatostatin receptor expression tumour volume (STV), total lesion somatostatin receptor expression (TLD, STV multiplied by SUV mean) and Tmean/Smean (SUVmean of tumours/metastases divided by SUVmean of normal spleen) were measured. Finally, the sum of STV (total STV, TSTV) and TLD (total TLD, TTLD) was calculated for each patient and used in the analysis.

Results: During the study period, 14 patients had stable disease (33.3%) and 28 patients experienced progression (66.7%), among whom 12 patients died. The median progression-free survival (PFS) and overall survival (OS) were 26.5 and 46.5 months, respectively. In the univariate and multivariate analysis, in the whole population study, Tmean/Smean ratio (HR 1.88, 95% CI 1.06-3.35, p = 0.03), Ki-67 index (HR 1.14, CI 1.03-1.26, p = 0.01) and pre-treatment chromogranin A serum concentration (HR 1.01, CI 1.0-1.03, p = 0.01) were significantly associated with PFS. Among patients with small intestinal NETs, TSTV (< 125.85 cm³ vs. ≥ 125.85 cm³, p = 0.023) and TTLD (< 4168.95 vs. ≥ 4168.95, p = 0.026) were significantly associated with PFS in the univariate analyses. No significant correlation was found between measured volumetric parameters and OS.

Conclusion: Volumetric parameters of pretreatment 68[Ga]Ga-DOTA-TATE PET/CT may be useful in prediction of the response to SSA (used in monotherapy as a first-line therapy) in patients with NET.

Background: Somatostatin receptor (SSR) targeting radiotracer ⁶⁸Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 ⁶⁸Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model's detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted.

Results: The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on ⁶⁸Ga- DOTATATE PET scans.

Conclusions: The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body ⁶⁸Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www.

Clinicaltrials: gov/study/NCT03206060 , https://www.

Clinicaltrials: gov/study/NCT04086485 , https://www.

Clinicaltrials: gov/study/NCT05012098 .

Background: Analysis of [18F]-Fluorodeoxyglucose (FDG) kinetics in cancer has been most often limited to the evaluation of the average uptake over relatively large volumes. Nevertheless, tumor lesions also contain inflammatory infiltrates whose cells are characterized by a significant radioactivity washout due to the hydrolysis of FDG-6P catalyzed by glucose-6P phosphatase. The present study aimed to verify whether voxel-wise compartmental analysis of dynamic imaging can identify tumor regions characterized by tracer washout. The study included 11 patients with lung cancer submitted to PET/CT imaging for staging purposes. Tumour was defined by drawing a volume of interest loosely surrounding the lesion and considering all inside voxels with a standardized uptake value (SUV) > 40% of the maximum. Eight whole-body scans were repeated after 20 min of dynamic imaging centered on the heart. Six parametric maps were generated progressively by computing a Patlak regression line for each voxel. Each analysis considered a different set of frames: starting with all eight frames, then the last seven frames, and so on, down to the last three frames.

Results: Delaying the starting point of the compartmental analysis revealed a progressive increase in the prevalence of voxels with a negative slope. In the most delayed parametric map, these voxels represented 0.5-4.5% (median 2%) of the tumor volume. This effect was independent of tumor size and was predominantly located at the lesion borders.

Conclusions: The voxel-wise parametric maps provided by compartmental analysis identify a measurable volume characterized by radioactivity washout. The spatial localization of this pattern is compatible with the recognized preferential site of inflammatory infiltrates populating the tumor stroma and might improve the power of FDG imaging in monitoring the effectiveness of treatments aimed at empowering the host immune response against cancer.

Trial registration: ClinicalTrials. The study was approved by the local ethical committee and it represented a single Institution ancillary trial within the expanded-access program for Nivolumab. NCT02475382. Registered 2015-06-16. URL: https://clinicaltrials.gov/study/NCT02475382?id=NCT02475382.&rank=1.

Background: Treatment of patients with low-grade and high-grade gliomas is highly variable due to the large difference in survival expectancy. New non-invasive tools are needed for risk stratification prior to treatment. The urokinase plasminogen activator receptor (uPAR) is expressed in several cancers, associated with poor prognosis and may be non-invasively imaged using uPAR-PET. We aimed to investigate the uptake of the uPAR-PET tracer [⁶⁸Ga]Ga-NOTA-AE105 in primary gliomas and establish its prognostic value regarding overall survival (OS), and progression-free survival (PFS). Additionally, we analyzed the proportion of uPAR-PET positive tumors to estimate the potential number of candidates for future uPAR-PRRT.

Methods: In a prospective phase II clinical trial, 24 patients suspected of primary glioma underwent a dynamic 60-min PET/MRI following the administration of approximately 200 MBq (range: 83-222 MBq) [⁶⁸Ga]Ga-NOTA-AE105. Lesions were considered uPAR positive if the tumor-to-background ratio, calculated as the ratio of TumorSUVmax-to-Normal-BrainSUVmean tumor-SUVmax-to-background-SUVmean, was ≥ 2.0. The patients were followed over time to assess OS and PFS and stratified into high and low uPAR expression groups based on TumorSUVmax.

Results: Of the 24 patients, 16 (67%) were diagnosed with WHO grade 4 gliomas, 6 (25%) with grade 3, and 2 (8%) with grade 2. Two-thirds of all patients (67%) presented with uPAR positive lesions and 94% grade 4 gliomas. At median follow up of 18.8 (2.1-45.6) months, 19 patients had disease progression and 14 had died. uPAR expression dichotomized into high and low, revealed significant worse prognosis for the high uPAR group for OS and PFS with HR of 14.3 (95% CI, 1.8-112.3; P = 0.011), and HR of 26.5 (95% CI, 3.3-214.0; P = 0.0021), respectively. uPAR expression as a continuous variable was associated with worse prognosis for OS and PFS with HR of 2.7 (95% CI, 1.5-4.8; P = 0.0012), and HR of 2.5 (95% CI, 1.5-4.2; P = 0.00073), respectively.

Conclusions: The majority of glioma patients and almost all with grade 4 gliomas displayed uPAR positive lesions underlining the feasibility of ⁶⁸Ga-NOTA-AE105 PET/MRI in gliomas. High uPAR expression is significantly correlated with worse survival outcomes for patients. Additionally, the high proportion of uPAR positive gliomas underscores the potential of uPAR-targeted radionuclide therapy in these patients.

Trail registration: EudraCT No: 2016-002417-21; the Scientific Ethics Committee: H-16,035,303; the Danish Data Protection Agency: 2012-58-0004; clinical trials registry: NCT02945826, 26Oct2016, URL: https://classic.

Clinicaltrials: gov/ct2/show/NCT02945826 .

Background: Imaging examination of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen is crucial for understanding the normal functioning and pathophysiology of the brain. A recently developed method estimates the appearance time of cerebral blood (ATB) pixel-wise from the imaging examination of CBF alone. In this study, we aimed to test the potential of ATB as an indicator of OEF.

Results: We retrospectively reviewed patients (n = 62) with suspected cerebrovascular disorders including steno-occlusive disease who underwent positron emission tomography (PET) with ¹⁵O-labelled tracers. Regarding the generated OEF and ATB images, a visual assessment was performed to test the consistency of the elevated OEF and delayed ATB. The OEF and ATB values and the absolute differences between their ipsilateral and contralateral sides were extracted and obtained for the entire hemisphere and the middle, anterior, and posterior cerebral arterial regions. Consistency was observed in 52 PET scans (83.9%) in visual assessment. The OEF and ATB values were moderately correlated (r = 0.553, p < 0.001), and the differences between their ipsilateral and contralateral sides were weakly correlated (r = 0.276, p < 0.001).

Conclusion: Our results indicate the potential of ATB as an indicator of OEF.

Background: Clinical application of the tracer net influx rate (Ki) imaging in PET/CT remains limited, due to a lack of evidence demonstrating the superiority of Ki images in lesion detection, and guidelines on when to utilize Ki images. This study aims to compare the benefits of Ki and standardized uptake value (SUV) images in lesion detection during PET/CT imaging. By analyzing the performance of both techniques in identifying tumor lesions, the study seeks to provide guidance for the clinical application of Ki images.

Results: This retrospective study included 134 patients with 244 pathologically confirmed lesions (200 malignant and 44 benign). Patients with a histopathological diagnosis received a weight-based ¹⁸F-FDG injection and underwent 60-min total-body PET/CT dynamic imaging. SUV images were reconstructed using data collected from the last 10 min of the scans. Ki images were generated using the Patlak methods with data from minutes 12-60. The background SUV_max, SUV_mean, SUV_SD, Ki_max, Ki_mean, and Ki_SD values were recorded. The signal-to-noise ratios of the SUV (SUV_SNR) and Ki (Ki_SNR) images were calculated. The lesion detection rate and sensitivity of the SUV and Ki images were evaluated. The lesion-detection rates were 97.7% (214/219) and 99.5% (218/219) for the SUV and Ki images, respectively (p = .22). Five false-negative lesions on the SUV images were true-positive on the Ki images (3 hepatic malignancies and 2 metastatic lymph nodes). The sensitivity (94.0% vs. 96.0%, p = .22), specificity (41.9% vs. 41.9%, p > .99), accuracy (84.4% vs. 86.1%, p = .61), positive predictive value (87.9% vs. 88.1%, p = .94), negative predictive value (60.0% vs. 69.2%, p = .47), and the area under the curve [0.68 (95% confidence interval, 0.61-0.73) vs. 0.69 (95% confidence interval, 0.62-0.74)] were similar in the SUV and Ki images (all p ≥ .10).

Conclusion: Ki images exhibit benefits in lesion detection compared to SUV images, particularly in organs with high background such as liver. The enhanced contrast provided by Ki imaging is recommended to clinically improve detection rates in such cases.

Background: The main objective is to discuss why treatment of non-prostate cancers with [¹⁷⁷Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time.

Case presentation: [⁶⁸Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [¹⁷⁷Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2-0.5 Gy. No treatment effect was achieved.

Conclusion: Rapid tumor washout of [¹⁷⁷Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [⁶⁸Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed.