Dataset Information

Feasibility and utility of MRI and dynamic ¹⁸F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer.

ABSTRACT:

Background

Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibility and utility of MRI and dynamic ¹⁸F-fluorodeoxyglucose (FDG)-PET imaging for monitoring tumor progression and assessing chemotherapy response in an orthotopic organoid-based patient-derived xenograft (O-PDX) mouse model of EC.

Methods

18 O-PDX mice (grade 3 endometrioid EC, stage IIIC1), selectively underwent weekly T2-weighted MRI (total scans = 32), diffusion-weighted MRI (DWI) (total scans = 9) and dynamic ¹⁸F-FDG-PET (total scans = 26) during tumor progression. MRI tumor volumes (vMRI), tumor apparent diffusion coefficient values (ADC_mean) and metabolic tumor parameters from ¹⁸F-FDG-PET including maximum and mean standard uptake values (SUV_max/SUV_mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of ¹⁸F-FDG (MR_FDG) were calculated. Further, nine mice were included in a chemotherapy treatment study (treatment; n = 5, controls; n = 4) and tumor ADC_mean-values were compared to changes in vMRI and cellular density from histology at endpoint. A Mann-Whitney test was used to evaluate differences between groups.

Results

Tumors with large tumor volumes (vMRI) had higher metabolic activity (MTV and TLG) in a clear linear relationship (r² = 0.92 and 0.89, respectively). Non-invasive calculation of MR_FDG from dynamic ¹⁸F-FDG-PET (mean MR_FDG = 0.39 μmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADC_mean (p = 0.03), lower vMRI (p = 0.03) and tumor cellular density (p = 0.02) than non-treated mice, all indicating treatment response.

Conclusion

Preclinical imaging mirroring clinical imaging methods in EC is highly feasible for monitoring tumor progression and treatment response in the present orthotopic organoid mouse model.

SUBMITTER: Espedal H

PROVIDER: S-EPMC8474962 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Project description:PurposeIn head and neck squamous cell carcinoma (HNSCC), the early diagnosis and efficient detection of recurrences and/or residual tumor after treatment play a very important role in patient's prognosis. Positron emission tomography (PET) using 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) has become an established method for the diagnosis of suspected recurrence in head and neck carcinomas. In particular, integrated PET/MRI imaging that provides optimal soft tissue contrast and less dental implant artifacts compared to PET/CT is an intriguing technique for the follow-up imaging of HNSCC patients. The aim of this study was to evaluate the benefit of PET/MRI compared to PET/CT in post-treatment follow-up imaging of HNSCC patients.MethodsThis retrospective observational cohort study consists of 104 patients from our center with histologically confirmed HNSCC. All patients received chemoradiotherapy (CRT) and underwent 18F-FDG-PET/CT (n = 52) or 18F-FDG-PET/MRI (n = 52) scan 12 weeks after the end of treatment. Image analysis was performed by two independent readers according to a five-point Likert scale analysis.ResultsPET/MRI was more sensitive (1.00 vs. 0.77) than PET/CT in the detection of locoregional recurrence. PET/MRI also had better negative (1.00 vs. 0.87) predictive values. AUCs for PET/MRI and PET/CT on patient-based analysis were 0.997 (95% CI 0.989-1.000) and 0.890 (95% CI 0.806-0.974), respectively. The comparison of sensitivity, AUCs, and negative predictive values revealed a statistically significant difference, p < 0.05. In PET/CT, false-negative and positive findings were observed in the more advanced disease stages, where PET/MRI performed better. Also, false-negative findings were located in the oropharyngeal, laryngeal, and nasopharyngeal regions, where PET/MRI made no false-negative interpretations.ConclusionBased on these results, PET/MRI might be considered the modality of choice in detecting locoregional recurrence in HNSCC patients, especially in the more advanced stages in the oral cavity, larynx, or nasopharynx.

Project description:BackgroundMagnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center.MethodsPatients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM.ResultsA total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively.Conclusions18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.

Project description:PurposeGlioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [18F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [18F]FET and [18F]fluciclovine using PET pharmacokinetic modeling (PKM).Methods[18F]rhPSMA-7.3, [18F]FET, and [18F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq (n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation.Results[18F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1-2.5, in 15-60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution VT (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [18F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and VS (1.3/0.7, p < 0.05, tumor) compared to [18F]FET and LA indicated reversible binding. VT increased (p < 0.001, tumor, 21 to 28 days) for [18F]FET (0.5-1.4) and [18F]fluciclovine (0.84-1.5).Conclusion[18F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [18F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [18F]fluciclovine was superior to [18F]FET rendering it more suitable for PET imaging of GBM.

Dataset Information

Feasibility and utility of MRI and dynamic ¹⁸F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer.

Background

Methods

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer.

Background

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Feasibility and utility of MRI and dynamic ¹⁸F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer.