Dataset Information

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [¹⁸F]FDG and sodium [¹⁸F]fluoride PET.

ABSTRACT:

Background

Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([¹⁸F] FDG) and sodium [¹⁸F] Fluoride (Na [¹⁸F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses.

Methods

Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [¹⁸F]FDG and Na [¹⁸F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10⁷ and 10⁸ pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [¹⁸F] FDG PET studies. [¹⁸F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [¹⁸F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques.

Results

The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [¹⁸F] FDG uptake, with a sensitivity and specificity of 100%. The [¹⁸F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [¹⁸F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [¹⁸F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [¹⁸F] FDG and Na [¹⁸F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [¹⁸F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10⁷ pfu dose.

Conclusions

PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [¹⁸F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01.

SUBMITTER: Collantes M

PROVIDER: S-EPMC6267920 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Coronary 18F-sodium fluoride (18F-NaF) PET identifies ruptured plaques in patients with recent myocardial infarction and localizes to atherosclerotic lesions with active calcification. Most studies to date have performed the PET acquisition 1 h after injection. Although qualitative and semiquantitative analysis is feasible with 1-h images, residual blood-pool activity often makes it difficult to discriminate plaques with 18F-NaF uptake from noise. We aimed to assess whether delayed PET performed 3 h after injection improves image quality and uptake measurements. Methods: Twenty patients (67 ± 7 y old, 55% male) with stable coronary artery disease underwent coronary CT angiography (CTA) and PET/CT both 1 h and 3 h after the injection of 266.2 ± 13.3 MBq of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, SUVmax, corrected SUVmax (cSUVmax), and target-to-background (TBR) ratio in lesions defined by CTA on 1-h versus 3-h 18F-NaF PET. Results: On 1-h PET, 26 CTA lesions with 18F-NaF PET uptake were identified in 12 (60%) patients. On 3-h PET, we detected 18F-NaF PET uptake in 7 lesions that were not identified on 1-h PET. The median cSUVmax and TBRs of these lesions were 0.48 (interquartile range [IQR], 0.44-0.51) and 1.45 (IQR, 1.39-1.52), respectively, compared with -0.01 (IQR, -0.03-0.001) and 0.95 (IQR, 0.90-0.98), respectively, on 1-h PET (both P < 0.001). Across the entire cohort, 3-h PET SUVmax was similar to 1-h PET measurements (1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], P = 0.30), and the background activity was lower (0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], P < 0.001). On 3-h PET, TBR, cSUVmax, and noise were significantly higher (respectively: 2.30 [IQR, 1.70-2.68] vs. 1.28 [IQR, 0.98-1.56], P < 0.001; 0.38 [IQR, 0.27-0.70] vs. 0.90 [IQR, 0.64-1.17], P < 0.001; and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). Median cSUVmax and TBR increased by 92% (range, 33%-225%) and 80% (range, 20%-177%), respectively. Conclusion: Blood-pool activity decreases on delayed imaging, facilitating the assessment of 18F-NaF uptake in coronary plaques. Median TBR increases by 80%, leading to the detection of more plaques with significant uptake than are detected using the standard 1-h protocol. A greater than 1-h delay may improve the detection of 18F-NaF uptake in coronary artery plaques.

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:This study characterized the distribution of [18 F]-sodium fluoride (NaF) uptake and blood flow in the femur and acetabulum in hip osteoarthritis (OA) patients to find associations between bone remodeling and cartilage composition in the presence of morphological abnormalities using simultaneous positron emission tomography and magnetic resonance imaging (PET/MR), quantitative magnetic resonance imaging (MRI) and femur shape modeling. Ten patients underwent a [18 F]-NaF PET/MR dynamic scan of the hip simultaneously with: (i) fast spin-echo CUBE for morphology grading and (ii) T1? /T2 magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots for cartilage, bone segmentation, bone shape modeling, and T1? /T2 quantification. The standardized uptake values (SUVs) and Patlak kinetic parameter (Kpat ) were calculated for each patient as PET outcomes, using an automated post-processing pipeline. Shape modeling was performed to extract the variations in bone shapes in the patients. Pearson's correlation coefficients were used to study the associations between bone shapes, PET outcomes, and patient reported pain. Direct associations between quantitative MR and PET evidence of bone remodeling were established in the acetabulum and femur. Associations of shaft thickness with SUV in the femur (p?=?0.07) and Kpat in the acetabulum (p?=?0.02), cam deformity with acetabular score (p?=?0.09), osteophytic growth on the femur head with Kpat (p?=?0.01) were observed. Pain had increased correlations with SUV in the acetabulum (p?=?0.14) and femur (p?=?0.09) when shaft thickness was accounted for. This study demonstrated the ability of [18 F]-NaF PET-MRI, 3D shape modeling, and quantitative MRI to investigate cartilage-bone interactions and bone shape features in hip OA, providing potential investigative tools to diagnose OA. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2671-2680, 2019.

Project description:This paper investigated whether positron emission tomography (PET) imaging with [18F]fludarabine ([18F]FDB) can help to differentiate central nervous system lymphoma (CNSL) from glioblastoma (GBM), which is a crucial issue in the diagnosis and management of patients with these aggressive brain tumors. Multimodal analyses with [18F]fluorodeoxyglucose ([18F]FDG), magnetic resonance imaging (MRI) and histology have also been considered to address the specificity of [18F]FDB for CNSL. Methods: Nude rats were implanted with human MC116 lymphoma-cells (n = 9) or U87 glioma-cells (n = 4). Tumor growth was monitored by MRI, with T2-weighted sequence for anatomical features and T1-weighted with gadolinium (Gd) enhancement for blood brain barrier (BBB) permeability assessment. For PET investigation, [18F]FDB or [18F]FDG (~11 MBq) were injected via tail vein and dynamic PET images were acquired up to 90 min after radiotracer injection. Paired scans of the same rat with the two [18F]-labelled radiotracers were investigated. Initial volumes of interest were manually delineated on T2w images and set on co-registered PET images and tumor-to-background ratio (TBR) was calculated to semi-quantitatively assess the tracer accumulation in the tumor. A tile-based method for image analysis was developed in order to make comparative analysis between radiotracer uptake and values extracted from immunohistochemistry staining. Results: In the lymphoma model, PET time-activity curves (TACs) revealed a differential response of [18F]FDB between tumoral and healthy tissues with average TBR varying from 2.45 to 3.16 between 5 to 90 min post-injection. In contrast, [18F]FDG demonstrated similar uptake profiles for tumoral and normal regions with TBR varying from 0.84 to 1.06 between these two time points. In the glioblastoma (GBM) model, the average TBRs were from 2.14 to 1.01 for [18F]FDB and from 0.95 to 1.65 for [18F]FDG. Therefore, inter-model comparisons showed significantly divergent responses (p < 0.01) of [18F]FDB between lymphoma and GBM, while [18F]FDG demonstrated overlap (p = 0.04) between the groups. Tumor characterization with histology (based mainly on Hoechst and CD79), as well as with MRI was overall in better agreement with [18F]FDB-PET than [18F]FDG with regard to tumor selectivity. Conclusions: [18F]FDB-PET demonstrated considerably greater specificity for CNSL when compared to [18F]FDG. It also permitted a more precise definition of target volume compared to contrast-enhanced MRI. Therefore, the potential of [18F]FDB-PET to distinguish CNSL from GBM is quite evident and will be further investigated in humans.

Dataset Information

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [¹⁸F]FDG and sodium [¹⁸F]fluoride PET.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [18F]FDG and sodium [18F]fluoride PET.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [¹⁸F]FDG and sodium [¹⁸F]fluoride PET.