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A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

ABSTRACT: The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

SUBMITTER: Yassin MA

PROVIDER: S-EPMC7647608 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

Yassin Mohamed A MA Nehmeh Sadek A SA Nashwan Abdulqadir J AJ Kohla Samah A SA Mohamed Shehab F SF Ismail Omar M OM Sabbagh Ahmad Al AA Ibrahim Firyal F Soliman Dina S DS Szabados Lajos L Fayad Hadi H

Medicine 20201101 45

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferati ...[more]

PMID: 33157979

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

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Project description:Objective [18F]Fluorocholine positron emission tomography/computed tomography (PET/CT) is used frequently in addition to [99mTc]Tc-Sestamibi scintigraphy and ultrasonography for the location of hyperfunctioning parathyroid glands. The aim of this study is to evaluate the performance of quantitative criteria in [18F]fluorocholine PET/CT for localization of hyperfunctioning parathyroid glands. The secondary objective is to highlight a correlation between the detection rate of [18F]fluorocholine PET/CT and serum parathyroid hormone (PTH) level. Materials and methods In two academic centers, we retrospectively included patients with biological hyperparathyroidism (HPT) and who had [18F]fluorocholine PET/CT. After a visual analysis, to measure the overall performance of [18F]fluorocholine PET/CT, a blind reading was carried out with standardized measurements of maximum standardized uptake value (SUVmax), liver ratio, thyroid ratio, and size ratio. We analyzed the quantitative criteria of [18F]fluorocholine PET/CT compared to the histological results, in particular to identify differences between adenomas and hyperplasias. We compared the performance of each quantitative criterion to the overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]fluorocholine PET/CT. The detection rate of hyperfunctioning parathyroid glands was calculated in subgroups of serum PTH level. Results The quantitative criteria in [18F]fluorocholine PET/CT were measured for 120 patients (135 lesions). The areas under the receiver operating characteristic (ROC) curve representing SUVmax and liver ratio were significantly increased. The optimal cut-off values represented by the maximum Youden index was >4.12 for SUVmax and >27.4 for liver ratio. Beyond certain threshold values of SUVmax (>4.12) or liver ratio (>38.1), all the lesions were histologically proven adenomas. SUVmax and liver ratio were significantly higher for adenomas than for hyperplasias and differential diagnosis (p = 0.0085 and p = 0.0002). The positivity of [18F]fluorocholine PET/CT was correlated with PTH level. Detection rates were 55.56, 75.56, and 87.5%, respectively, for serum PTH < 70, 70 to 120, and >120 ng/ml. Conclusion Semi-quantitative measurements (SUVmax and liver ratio) should be considered as additional tools in interpretation of [18F]fluorocholine PET/CT. These quantitative parameters have lower overall performance but higher specificity than overall visual analysis in identifying an adenoma. Above certain threshold values, all lesions are adenomas. [18F]fluorocholine PET/CT confirms excellent performance for the detection of hyperfunctional parathyroids. For serum PTH levels < 70 ng/ml, the detection rate of [18F]fluorocholine PET/CT is strongly decreased.

Dataset Information

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

Publications

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

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