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

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heidi Espedal ◽  
Hege F. Berg ◽  
Tina Fonnes ◽  
Kristine E. Fasmer ◽  
Camilla Krakstad ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mouse Model ◽  
Tumor Progression ◽  
Treatment Response ◽  
Fdg Pet ◽  
Whole Body ◽  
Chemotherapy Response ◽  
Pelvic Magnetic Resonance Imaging ◽  
Imaging Methods ◽  
Cellular Density

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 (ADCmean) and metabolic tumor parameters from 18F-FDG-PET including maximum and mean standard uptake values (SUVmax/SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of 18F-FDG (MRFDG) were calculated. Further, nine mice were included in a chemotherapy treatment study (treatment; n = 5, controls; n = 4) and tumor ADCmean-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 MRFDG from dynamic 18F-FDG-PET (mean MRFDG = 0.39 μmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADCmean (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.

scholarly journals Feasibility and Utility of MRI and Dynamic 18F-FDG-PET in An Orthotopic Organoid-Based Patient-Derived Mouse Model of Endometrial Cancer

2021 ◽  
Author(s):  
Heidi Espedal ◽  
Hege Fredriksen Berg ◽  
Tina Fonnes ◽  
Kristine Eldevik Fasmer ◽  
Camilla Krakstad ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mouse Model ◽  
Tumor Progression ◽  
Treatment Response ◽  
Fdg Pet ◽  
Whole Body ◽  
Pelvic Magnetic Resonance Imaging ◽  
Imaging Methods ◽  
Cellular Density ◽  
Spearman Test

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-fluorodeoxyglucoce (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: 19 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 (ADCmean) and metabolic tumor parameters from 18F-FDG-PET including maximum and mean standard uptake values (SUVmax/SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of 18F-FDG (MRFDG) were calculated. Correlation between imaging parameters was assessed using a two-tailed Spearman test. Further, nine mice were included in a chemotherapy treatment study (treatment; n=5, controls; n=4) and tumor ADCmean-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 significantly higher metabolic activity (MTV and TLG; r=0.93, p<0.0001). Non-invasive calculation of MRFDG from dynamic 18F-FDG-PET (mean MRFDG=0.39 mmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADCmean (p=0.03) and 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.

[68Ga]RGD Versus [18F]FDG PET Imaging in Monitoring Treatment Response of a Mouse Model of Human Glioblastoma Tumor with Bevacizumab and/or Temozolomide

2018 ◽  
Vol 21 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Claire Provost ◽  
Laura Rozenblum-Beddok ◽  
Valérie Nataf ◽  
Fatiha Merabtene ◽  
Aurélie Prignon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Treatment Response ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Human Glioblastoma ◽  
18F Fdg ◽  
Monitoring Treatment ◽  
Monitoring Treatment Response

Phase II and fluorodeoxyglucose positron emission tomography (FDG-PET) study in patients with advanced biliary tract cancers (BTCs) receiving bevacizumab (B) in combination with gemcitabine (GEM) and oxaliplatin (OX)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
A. X. Zhu ◽  
J. A. Meyerhardt ◽  
L. S. Blaszkowsky ◽  
A. Muzikansky ◽  
T. A. Abrams ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Phase Ii ◽  
Fdg Pet ◽  
Performance Status ◽  
Progression Free Survival ◽  
Whole Body ◽  
Eligibility Criteria ◽  
Positron Emission ◽  
The Difference ◽  
Pre Treatment

4578 Background: Vascular endothelial growth factor (VEGF) expression is present in BTCs and is associated with poor survival. We performed a phase II study to examine the efficacy and tolerability of GEM and OX in combination with B (GEMOX-B) in patients (pts) with advanced BTCs. We also assessed the use of FDG-PET as an early indicator of response following treatment. Methods: Eligibility criteria included unresectable or metastatic measurable BTCs, 0–1 prior chemotherapy regimens, performance status ≤ 2, and adequate organ functions. Pts were treated with all 3 drugs intravenously on days 1 and 15 every 28 days (one cycle): B was given first at 10 mg/kg, followed by GEM at 1000 mg/m2 as a dose-rate infusion at 10 mg/m2/minute, and OX at 85 mg/m2. Whole body FDG-PET scan was obtained at baseline and at the end of cycle 2. The primary endpoint of the study was progression-free survival (PFS). Results: The planned 35 pts (25 cholangiocarcinoma and 10 gallbladder carcinoma) were enrolled: median age = 60 (25–82), M/F = 21/14, median ECOG 1. All pts were evaluable for toxicity and 29 were evaluable for response. Treatment related grade 3–4 toxicities included neutropenia (20%), ALT (17%), neuropathy (14%), hypertension (11%), AST (9%), anorexia (9%), and thrombocytopenia (9%). 13 pts (45%) had a partial response (PR) and an additional 10 pts (34%) had stable disease (SD). With a median follow up of 9.9 months, the median overall survival was 13.2 months (95% CI, 7.3 to 20.5 months), and the median PFS was 7.0 months (95% CI, 5.4 to 9.6 months). The mean baseline SUVmax was 5.72±2.01 and post-treatment SUVmax was 3.73±1.88 with a median 36.4% decrease (n=32). The difference in SUV changes between the groups with PR/SD and progressive disease was statistically significant (p=0.006). An increase in adjusted post- to pre-treatment SUV increased the risk for tumor progression (hazard ratio=3.054). Conclusions: GEMOX-B demonstrated significant antitumor activity with tolerable safety profiles in patients with advanced BTCs. FDG-PET showed significant early decreases in SUVmax following treatment, and these changes correlated with tumor response and time to tumor progression. [Table: see text]

Abstract 2726: Tumor progression and treatment response characterization in a novel mouse model of colon cancer.

2013 ◽  
Author(s):  
Jamie N. Hadac ◽  
Terrah J. Paul Olson ◽  
Michael A. Newton ◽  
Gregory D. Kennedy ◽  
William R. Schelman ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mouse Model ◽  
Tumor Progression ◽  
Treatment Response

Assessment of local control after laser-induced thermotherapy of liver metastases from colorectal cancer: contribution of FDG-PET in patients with clinical suspicion of progressive disease

2007 ◽  
Vol 48 (8) ◽  
pp. 821-830 ◽  
Author(s):  
T. Denecke ◽  
I. Steffen ◽  
B. Hildebrandt ◽  
R. Rühl ◽  
F. Streitparth ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Progression ◽  
Local Control ◽  
Fdg Pet ◽  
Colorectal Liver Metastases ◽  
Progressive Disease ◽  
Systemic Disease ◽  
Clinical Suspicion ◽  
Whole Body ◽  
Promising Alternative

Background: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Purpose: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. Material and Methods: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semiquantitatively (maximal standard uptake value [SUVmax], tumor-to-normal ratio [T/N]). The standard of reference was histopathology ( n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. Results: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUVmax (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients ( P = 0.007). Conclusion: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with LITT.

scholarly journals Immune Checkpoint Inhibitors in Advanced NSCLC: [18F]FDG PET/CT as a Troubleshooter in Treatment Response

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1681
Author(s):  
Cristina Ferrari ◽  
Giulia Santo ◽  
Nunzio Merenda ◽  
Alessia Branca ◽  
Paolo Mammucci ◽  
...  
Keyword(s):  
Treatment Response ◽  
Lymphoid Cell ◽  
Fdg Pet ◽  
Checkpoint Inhibitors ◽  
Whole Body ◽  
Quantitative Parameters ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Nsclc Patients

Introduction: The aim of this study was to investigate whether [18F]FDG PET/CT-derived semi-quantitative parameters can predict immunotherapy treatment response in non-small cell lung cancer (NSCLC) patients. Secondly, immune-related adverse events (irAEs) and lymphoid cell-rich organs activation were evaluated. Materials and Methods: Twenty-eight patients who underwent [18F]FDG PET/CT scans before and at first restaging therapy with immuno-checkpoint inhibitors (ICIs) were retrospectively analyzed. PET-based semi-quantitative parameters extracted from both scans were respectively: SUVmax and SUVpeak of the target lesion, whole-body metabolic tumor volume (MTVWB), and whole-body total lesion glycolysis (TLGWB), as well as their interval changes (ΔSUVmaxTL, ΔSUVpeakTL, ΔMTVWB, ΔTLGWB). These PET-derived parameters were correlated to controlled disease (CD) assessed by RECIST 1.1. IrAEs, if present, were also described and correlated with clinical benefit (CB). SUVmax of the spleen and bone marrow at restaging scans were also correlated to CB. Results: The CD was achieved in 54% of patients. Out of 28 eligible patients, 13 (46%) experienced progressive disease (PD), 7 showed SD, 7 had PR, and only in one patient CR was achieved. ΔSUVmaxTL (p = 0.002) and ΔSUVpeakTL (p < 0.001) as well as ΔMTVWB (p < 0.001) and ΔTLGWB (p < 0.005) were significantly associated with PD vs. non-PD. IrAEs and lymphoid cell-rich organs activation did not correlate with CB. Conclusions: [18F]FDG PET/CT by using interval changes of PET-derived semi-quantitative parameters could represent a reliable tool in immunotherapy treatment response evaluation in NSCLC patients.

scholarly journals [18F]FDG PET/CT Studies in Transgenic Hualpha-Syn (A53T) Parkinson’s Disease Mouse Model of α-Synucleinopathy

2021 ◽  
Vol 15 ◽  
Author(s):  
Rommani Mondal ◽  
Anthony-David Tawatao Campoy ◽  
Christopher Liang ◽  
Jogeshwar Mukherjee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Fdg Pet ◽  
Whole Body ◽  
Suitable Model ◽  
Male And Female ◽  
Fdg Uptake ◽  
Pet Ct ◽  
Fdg Pet Ct

Transgenic mice line M83 that express the A53T mutant α–synuclein protein at six times the level of endogenous mice α–synuclein are a model of α-synucleinopathy found in Parkinson’s disease (PD). This Hualpha-Syn (A53T) PD model is useful in assessing non-motor deficits at earlier stages of onset of PD. We report findings on metabolic changes using [18F]FDG PET/CT in the Hualpha-Syn (A53T) PD mouse model in comparison to non-carrier mice. Whole-body PET/CT imaging of male and female mice were carried out 2 h after [18F]FDG ip administration under 3% isoflurane anesthesia. Brain images were analyzed with PET images coregistered to a mouse brain MRI template. Hualpha-Syn (A53T) mice had significantly lower [18F]FDG uptake in several brain regions compared to the no-carrier mice. Significant hind limb muscle and lower spinal cord [18F]FDG hypometabolism at 9 months of age in A53T PD mice was also indicative of neurodegenerative disease, with a progressive motoric dysfunction leading to death. Significant decrease (up to 30%) in [18F]FDG uptake were observed in 9-month old male and female Hualpha-Syn (A53) mice. This is consistent with the cortical hypometabolism in PD patients. Hualpha-Syn (A53) mice may thus be a suitable model for studies related to PD α-synucleinopathy for the discovery of new biomarkers.

scholarly journals Prospective Comparison of 18-FDG PET/CT and Whole-Body MRI with Diffusion-Weighted Imaging in the Evaluation of Treatment Response of Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1938
Author(s):  
Charles Mesguich ◽  
Valérie Latrabe ◽  
Cyrille Hulin ◽  
Axelle Lascaux ◽  
Laurence Bordenave ◽  
...  
Keyword(s):  
Treatment Response ◽  
Fdg Pet ◽  
Diffusion Weighted Imaging ◽  
Whole Body ◽  
Newly Diagnosed ◽  
Whole Body Mri ◽  
Post Induction ◽  
Imaging Results ◽  
Pet Ct ◽  
Fdg Pet Ct

To compare the prognostic values of 18-FDG PET/CT (FDG-PET) and Whole-Body MRI with Diffusion-Weighted Imaging (WB-DW-MRI) in the evaluation of treatment response of Multiple Myeloma (MM) patients eligible for ASCT. Thirty patients with newly diagnosed MM prospectively underwent FDG-PET and WB-DW-MRI at baseline, after induction chemotherapy and after ASCT. Response on WB-DW-MRI was evaluated with the MY-RADS criteria. FDG-PET was considered positive if residual uptake was superior to liver uptake. Imaging results were not used for treatment modification. The impact of imaging results on PFS was analyzed. After a median follow-up of 32 months, 10 patients relapsed. With WB-DW-MRI, post-induction examination was positive in 3/25 and post-ASCT examination was positive in 3/27 patients. However, neither study showed prognostic impact on PFS. FDG-PET was positive in 5/22 post-induction and 3/26 patients post-ASCT, respectively. Positivity of FDG-PET, post-induction or post-ASCT, was associated with a shorter PFS (post-induction: median PFS 19 months vs. not reached, log-rank p = 0.0089; post-ASCT: median PFS 18 months vs. not reached, log-rank p = 0.0005). Preliminary results from this small, single-center, prospective study show that, whether performed post-induction or post-ASCT, FDG-PET has a higher prognostic value than WB-DW-MRI for treatment response evaluation of newly diagnosed MM.

scholarly journals Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1885 ◽  
Author(s):  
Heidi Espedal ◽  
Tina Fonnes ◽  
Kristine E. Fasmer ◽  
Camilla Krakstad ◽  
Ingfrid S. Haldorsen
Keyword(s):  
Computed Tomography ◽  
Endometrial Cancer ◽  
Tumor Progression ◽  
Photon Emission ◽  
Model Systems ◽  
Imaging Biomarkers ◽  
In Vivo Model ◽  
Emission Computed Tomography ◽  
Preclinical Imaging ◽  
Imaging Methods

Endometrial cancer is the most common gynecologic malignancy in industrialized countries. Most patients are cured by surgery; however, about 15% of the patients develop recurrence with limited treatment options. Patient-derived tumor xenograft (PDX) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification. Preclinical imaging by magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), single-photon emission computed tomography (SPECT) and optical imaging during disease progression enables visualization and quantification of functional tumor characteristics, which may serve as imaging biomarkers guiding targeted therapies. A critical question, however, is whether the in vivo model systems mimic the disease setting in patients to such an extent that the imaging biomarkers may be translatable to the clinic. The primary objective of this review is to give an overview of current and novel preclinical imaging methods relevant for endometrial cancer animal models. Furthermore, we highlight how these advanced imaging methods depict pathogenic mechanisms important for tumor progression that represent potential targets for treatment in endometrial cancer.

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