The role of 18F-FDG PET in the assessment of a benign hematological disorder: polycythemia.

Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging was conceived in the early 1970 by investigators at the University of Pennsylvania as a research technique to measure brain metabolism and function by employing a non-invasive imaging approach. Soon after the introduction of whole-body PET instruments, 18F-FDG was utilized in the assessment of a variety of solid tumors and certain hematological malignancies. Yet, the role of 18F-FDG in assessing benign and uncommon malignant disorders of the bone marrow has not been investigated to a great extent. Fluorine-18-FDG as a molecular probe has the proven capacity to reflect the abnormal glycolytic activities inherent to a variety of disorders, where such information may serve as a guide to the clinical course of the respective disease. Recent efforts have studied bone marrow and extra-medullary disease activity in certain malignancies like chronic lymphocytic leukemia. Nonetheless, few studies have explored the role of 18F-FDG in assessing the metabolic basis of benign disorders of red marrow. Moreover, the introduction of novel imaging analysis schemes in recent years has allowed for the global assessment of red marrow disease, which can provide a superior means for characterizing the systemic nature and burden of these disorders. Accordingly, semi-quantitative global analysis techniques as applied to the skeletal structures in 18F-FDG PET may provide a tool to better understand these complex marrow abnormalities. Functional imaging of red bone marrow may also reveal critical information specifically regarding the extra-medullary extension of such hematological disorders that cannot be assessed by other diagnostic or imaging techniques. Myleoproliferative neoplasms (MPN) are an apt category of hematological disease that confer significantly altered systemic metabolic rates of hematopoietic stem cells (HSC) in the marrow, as such they are primed for exploration with 18F-FDG PET. The hallmark of such disorders involves the excess production of particular cellular components in blood. After a period of excess production, scar tissue may develop in place of the HSC leading to myleofibrosis and decreased hematopoietic activity. One of the least studied disorders within the larger category of MPN with respect to the nuclear medicine is polycythemia. Polycythemia may be either primary, polycythemia vera (PV), or secondary. PV involves a JAK2+ in HSC which allows for the excessive proliferation of immature erythrocytes and depressed erythropoietin levels as a result. Secondary polycythemia occurs in response to decreased oxygen intake, often as a result of smoking, which results in increased erythropoietin and hematocrit levels. Primary and secondary polycythemia lead to an increase in overall red marrow activity and a diffusion of active red marrow into the appendicular skeleton. Clinical presentation often includes redness or irritation of the skin along with headache, fatigue and excessive bleeding. Based upon the mentioned precedent, it is evident that PET imaging with 18F-FDG and other tracers will play a meaningful role in assessing diffuse bone marrow disorders such as hematological malignancies and myeloproliferative abnormalities. Semi-quantification studies of global bone marrow activity in such an application will be a vital means in accurately assessing the systematic nature and global burden of such benign hematological disorders such a polycythemia. Accordingly, the derived metabolic data projects to be a useful tool in the prospective clinical and scientific aspects of the diagnosis of these benign hematological disorders and the assessment of disease progression in light of relevant biological treatments. Given the nature of the disease and the enumerated capabilities of 18F-FDG PET it is expected that one would be able to capture the systematic abnormalities inherent to the disease. Moreover, the handful of case studies supports this possibility. Three case studies have all illustrated diffuse elevated 18F-FDG uptake throughout the axial and appendicular skeleton that reflects the hyper-metabolic red bone marrow as related to polycythemia. Moreover, the use of various functional imaging tracers, in addition to 18F-FDG, may indirectly reflect hypermetabolism in red bone marrow through abnormal tracer accumulation in the skeletons of patients. The whole body 18F-FDG scan of a JAK2+ PV patient before treatment (a) as compared to a matched subject (b) is found below; of note is the PV patient's elevated uptake in the pelvis, femur and spine.

Association between age, uptake of 18F-fluorodeoxyglucose and of 18F-sodium fluoride, as cardiovascular risk factors in the abdominal aorta.

OBJECTIVE: We aimed to assess the feasibility of quantifying fluorine-18-fluorodexoglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) uptake in abdominal aorta and examine their association with age and cardiovascular risk factors. SUBJECTS AND METHODS: Our study comprised 123 subjects (48±14 years of age, 62 men) including 78 healthy volunteers and 45 patients with chest pain syndrome, who originally enrolled in the CAMONA study in Odense, Denmark (NCT01724749). All subjects underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and 18F-NaF PET/CT on separate days, 180min and 90min after administration of tracers, respectively. The global tracer uptake value (GTUV) in the abdominal aorta was determined as sum of the product of each slice area and its corresponding average standardized uptake value (SUV mean), divided by the sum of those slice areas. In addition, for each subject, the 10 years Framingham risk score (FRS) was calculated. The correlations between 18F-NaF and 18F-FDG GTUV with age and 10 years FRS were assessed in all, healthy and patient subjects. RESULTS: There was a significant, positive correlation between subjects' age and 18F-NaF GTUV (r=0.35, P<0.001), but not 18F-FDG GTUV (r=0.06, P=0.53). Also, there was a significant, positive correlation between 10 years FRS and 18F-NaF GTUV (r=0.30, P<0.001), but not 18F-FDG GTUV (r=0.01, P=0.95). Individual differences in 18F-FDG and 118F-NaF uptake were large in both healthy subjects and patients. CONCLUSION: In this study, the global uptake of 18F-NaF in abdominal aorta was positively associated with age and 10 years FRS in all subjects, healthy and patient groups, whereas the global uptake of 18F-FDG was not.

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

PURPOSE: The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. PATIENTS AND METHODS: A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. RESULTS: There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. CONCLUSION: We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.