18f-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (PET/CT) for Assessment of Bone Marrow Metabolism in Patients with Myelofibrosis
Authors: Derlin Thorsten , Alchalby Haefaa , Bannas Peter , Veldhoen Simon , Büsche Guntram , Triviai Ioanna N , Bengel Frank , Kröger Nicolaus 
Published: October 2019

Abstract
Introduction Myelofibrosis is a hematopoetic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary hematopoiesis. Myelofibrosis is associated with a chronic inflammatory state, including, but not limited to the bone marrow space. Chronic inflammation is triggering the initiation of fibrogenesis, and bone marrow fibrosis is a hallmark of terminal phase myelofibrosis. Positron emission tomography/computed tomography (PET/CT) using the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) is widely used for imaging of both inflammatory and malignant processes due to increased glucose consumption in inflammatory and neoplastic cells. A noninvasive method to visualize and quantify the extent of active myelofibrosis would be highly desirable, e.g. for therapy monitoring studies. Therefore, the aim of this study was to assess if 18F-FDG PET/CT provides noninvasive insights into the metabolic implications of the disease.
Methods In 30 patients, the biodistribution of the glucose analogue 18F-FDG was analyzed 60 min after intravenous injection of 350 MBq of 18F-FDG. The extent of bone marrow involvement was graded using a four-point scale. Bone marrow metabolism was quantified by measuring the mean and maximum standardized uptake value (SUV) in the bone marrow space. Imaging findings were compared with laboratory, cytogenetic and histopathological data.
Results Retention of 18F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, and 4 different patterns could be found. Ten (33.3%) of the 30 patients showed only mildly increased 18F-FDG uptake in the central skeleton and the proximal extremities (PET grade 1). Three (10%) patients showed markedly increased tracer uptake in the central skeleton and the proximal extremities extending into the distal half of the femoral bone (PET grade 2). In 8 (26.7%) patients, increased tracer uptake in the central skeleton and the extremities extending into the tibial bone was found (PET grade 3). Nine (30.0%) patients demonstrated increased 18F-FDG uptake in the central skeleton and the extremities extending into the small bones of the feet (PET grade 4). Extent of bone marrow involvement (PET grade) decreased over time from initial diagnosis (rs = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (rs = -0.37, p = 0.04) and as splenic volume increased (rs = -0.40, p = 0.03). There was a significant positive correlation between the metabolic activity of the bone marrow and splenic metabolic activity (p = 0.04), indicating that splenic uptake is parainflammatory.
Conclusions 18F-FDG PET/CT emerges as a promising technique for visualization and quantitation of bone marrow metabolism in myelofibrosis. We conclude that the increased bone marrow metabolism mainly reflects inflammatory activity within the bone marrow space. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET.

Disclosures
No relevant conflicts of interest to declare.