EJNMMI Research最新文献

Background: The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC).

Methods: One hundred and twenty-eight BC patients underwent a ¹⁸F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours.

Results: In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value<0.01) higher than C models and better than C+M+BF models (mean balanced accuracy of 0.66, 0.61, and 0.64 respectively). For HER2 tumours, equal performances were noted for C and C+M models, with performances higher than C+M+BF models (mean balanced accuracy of 0.64, and 0.61 respectively). Regarding TN tumours, the best classification results were reported for C+M models, with better performances than C and C+M+BF models but not significantly (mean balanced accuracy of 0.65, 0.63, and 0.62 respectively).

Conclusion: Baseline clinical data combined with global and texture tumour metabolism parameters assessed by ¹⁸F-FDG PET/CT provide a better prediction of pCR after NAC in patients with BC compared to clinical parameters alone for TN, and HER2 and TN tumours together. In contrast, adding BF parameters to the models did not improve prediction, regardless of the tumour subgroup analysed.

Background: N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). ¹²³I- and ¹⁸F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [¹⁸F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [¹⁸F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [¹⁸F]FP-CIT and its efficacy for PD diagnosis using murine models.

Results: Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [¹⁸F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [¹⁸F]FP-CIT injection. [¹⁸F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [¹⁸F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [¹⁸F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011).

Conclusions: This study fills the gap regarding insufficient preclinical studies on [¹⁸F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [¹⁸F]FP-CIT excretion, provide complementary evidence that [¹⁸F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.

Background: O-(2-[¹⁸F]fluoroethyl)-L-tyrosine positron emission tomography ([¹⁸F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test-retest variation of [¹⁸F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [¹⁸F]FET-PET metrics and to assess the impact of protein-intake prior to [¹⁸F]FET PET scanning of gliomas.

Results: Test-retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and - 0.13 (+ 9.7% and - 9.0%) for mean tumour-to-background ratio (TBR_mean), + 0.43 and - 0.28 (+ 19.6% and - 11.8%) for maximal tumour-to-background ratio (TBR_max), and + 2.14 cm³ and - 1.53 ml (+ 219.8% and - 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the L-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV - 25%) and in tumour (maximal SUV - 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBR_mean and TBR_max were only borderline significant, and changes generally within the variability observed in the group with no protein intake.

Conclusion: The test-retest repeatability was found to be good, and better for TBR_max and TBR_mean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [¹⁸F]FET PET scan decreases uptake of [¹⁸F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.

Background: Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [¹⁸F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis.

Methods: After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [¹⁸F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [¹⁸F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUV_mean) was calculated.

Results: PET signals revealed that in areas with evident lesions on CT, the SUV_mean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUV_mean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [¹⁸F]F-FAPI-42 binding to activated fibroblasts.

Conclusion: [¹⁸F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

Background: In preclinical studies, the positron emission tomography (PET) imaging with [¹¹C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [¹¹C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.

Results: Twelve healthy subjects underwent 90-min baseline [¹¹C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [¹¹C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [¹¹C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.

Conclusions: [¹¹C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.

Background: Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging.

Methods: In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (⁶⁸Ga-NOTA-RM26 and ⁶⁸Ga-NOTA-PSMA617) PET/CT.

Results: In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of ⁶⁸Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of ⁶⁸Ga-NOTA-RM26 than those with high GS (P = 0.001).

Conclusions: This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.

Background: Fatty acid uptake can be measured using PET and 14-(R,S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid ([¹⁸F]FTHA). However, the relatively rapid rate of [¹⁸F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [¹⁸F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [¹⁸F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [¹⁸F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [¹⁸F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.

Results: The new TLC method separated seven [¹⁸F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [¹⁸F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [¹⁸F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.

Conclusions: The newly developed improved radio-TLC method for [¹⁸F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [¹⁸F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [¹⁸F]FTHA metabolic rate under different study settings.

Trial registration: EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.

Clinicaltrials: gov/ct2/show/NCT05132335 .

Background: Neuroblastoma is the most common extra-cranial pediatric solid tumor. ¹³¹I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with ¹³¹I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma.

Results: Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of ¹³¹I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels.

Conclusion: The combination of AURKA inhibition with ¹³¹I-MIBG treatment is active in resistant neuroblastoma models.

Background: F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.

Methods: 191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax_CLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmax_CLN was estimated using linear regression models.

Results: Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax_CLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax_CLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax_CLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.

Conclusion: SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.

Trial was registered: In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.

Background: 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [¹⁸F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation.

Methods: Patients with MM who underwent a baseline [¹⁸F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [¹⁸F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [¹⁸F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively.

Results: A total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen's kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen's kappa 0.56 and 0.53, respectively). Among [¹⁸F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004-1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90-191.95), P = 0.01].

Conclusion: Our work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [¹⁸F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [¹⁸F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS.