18F-sodium Fluoride Positron Emission Research Articles

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Prostate-Specific Antigen and Prostate-Specific Antigen Kinetics in Predicting 18F-Sodium Fluoride Positron Emission Tomography-Computed Tomography Positivity for First Bone Metastases in Patients with Biochemical Recurrence after Radical Prostatectomy.

We evaluated the association between serum prostate specific antigen (PSA) level and kinetics to predict 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) positivity for first bone metastases in men with biochemical recurrence after radical prostatectomy. All 18F-NaF PET-CT scans that were performed at our institution during 2010–2014 were queried to find patients who demonstrated biochemical recurrence after radical prostatectomy. Records were reviewed to obtain data on PSA levels and kinetics at the time of 18F-NaF PET-CT and pathologic features of the prostatectomy specimen, which were then used for receiver operating characteristic (ROC) analysis to determine predictability for 18F-NaF PET positivity. Thirty-six patients met our inclusion criteria. Of these, 8 (22.2%) had positive 18F-NaF PET-CT scans. Mean values for PSA, PSA doubling time (PSADT), and PSA velocity (PSAV) were 2.02 ng/ml (range: 0.06–11.7 ng/ml), 13.2 months (range: 1.11–60.84), and 1.28 ng/ml/year (range: 0.1–5.28) for 18F-NaF PET-CT negative scans, and 4.11 ng/ml (range: 0.04–14.38 ng/ml), 8.9 months (range; 0.7–27.8), and 9.06 ng/ml/year (range: 0.04–50.2) for 18F-NaF PET-CT positive scans, respectively (P = 0.07, 0.47, and 0.02, respectively, for PSA, PSADT, and PSAV). ROC analysis for 18F-NaF PET-CT positivity resulted in area under the curve (AUC) values of 0.634 for PSA, 0.598 for PSADT, and 0.688 for PSAV. ROC analysis with combined models gave AUC values of 0.723 for a combination of PSA and PSADT, 0.689 for a combination of PSA and PSAV, and 0.718 for grouping of PSA, PSADT, and PSAV. There was no significant association between 18F-NaF PET-CT positivity and primary tumor Gleason score, TN staging, and status of surgical margins. 18F-NaF PET-CT detected first-time osseous metastases in 22.2% of our patients with biochemical recurrence after prostatectomy with the PSA level range ≤11.7 ng/ml. PSAV was statistically significant in predicting 18F-NaF PET-CT positivity. ROC analysis demonstrated higher AUCs when PSA was combined with PSA kinetics parameters.

Assessment of cardiac amyloidosis by using 18f-sodium fluoride PET/MR imaging

Purpose Cardiac amyloidosis exists in two predominant forms called acquired monoclonal immunoglobulin light-chain (AL) and transthyretin-related (ATTR). Their differentiation is a real diagnostic challenge for treatment management and prognosis of patient. Magnetic resonance (MR) imaging is increasingly used to aid in the diagnosis of cardiac amyloidosis on the basis of characteristic appearances on late Gadolinium enhancement (LGE) but cannot distinguish ATTR and Al forms. Several series have showed that scintigraphy using bone 99mTc-bisphosphonate tracers preferentially bind ATTR versus AL myocardial deposit. Our aim was to use 18F-Sodium Fluoride (18F-NaF) positron emission tomography (PET) bone tracer in hybrid PET/MR imaging to aid in both the diagnosis of cardiac amyloidosis and differentiation of ATTR and AL forms within a single scan. Methods Consecutive patients with biopsy-proven ATTR or AL cardiac amyloidosis and as many healthy control subjects were included. All patients underwent simultaneous PET/MR (BiographTM mMR, Siemens) scans after IV injection of 370MBq of 18F-NaF. The selected data were reconstructed using a 3D breath-hold Dixon MR attenuation correction map. MR protocol included LGE sequences, pre- and post-contrast T1 mapping. Maximal target-to-background ratio (TBRmax) was recorded, defined as maximal myocardial FDG uptake (SUVmax) corrected for mean right atrium blood pool activity. Mean TBRmax in ATTR, AL and controls were compared using a Student t-test. The institutional review board approved the study and all patients gave written informed consent. Results Eighteen patients (61.3 ± 10.5 yo, 12 M/6F) were prospectively recruited (6 ATTR, 3 AL and 9 controls). All amyloid patients had characteristic LGE appearances. Mean TBRmax were respectively 1.29 ± 0.31, 0.77 ± 0.06 and 0.68 ± 0.03 in ATTR, AL and control subjects. Mean TBRmax was significantly higher in ATTR than in AL patients ( P = 0.028) and in controls ( P = 0.0001). Mean TBRmax was significantly higher in AL patients than in controls ( P = 0.046). A TBRmax threshold of 0.85 appeared to differentiate all patients as having ATTR amyloidosis. There was no significant difference in terms of pre-contrast ( P = 0.48) and post-contrast T1 mapping ( P = 0.57) between ATTR and AL patients. Conclusion These results showed the potential of 18F-NaF PET/MR to diagnose cardiac amyloidosis and to differentiate ATTR and AL forms, confirming our preliminary published results (Trivieri et al. JACC 2016)

18F-sodium fluoride positron emission tomography for molecular imaging of coronary atherosclerosis based on computed tomography analysis

Background and aimsWe aimed at evaluating the relation of 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography (PET) to coronary atherosclerosis detected and assessed by computed tomography (CT). MethodsThirty-two patients with one or more coronary atherosclerotic lesions detected on cardiac CT underwent 18F-NaF PET/CT. Each coronary atherosclerotic lesion was evaluated on CT angiography for plaque types (calcified plaque [CP], non-calcified plaque [NCP], partially calcified plaque [PCP]), and the presence of CT-based high-risk features (minimum CT density <30 Hounsfield units and vascular remodeling index >1.1). Focal 18F-NaF uptake of each lesion was quantified using maximum tissue-to-background ratio (TBRmax). ResultsA total of 111 lesions were studied. In a patient-based analysis, logarithmically transformed coronary calcium score correlated positively with maximum TBRmax per patient, and 15 patients with myocardial infarction or unstable angina history showed a higher maximum TBRmax per patient than those without (1.36 ± 0.15 versus 1.15 ± 0.15, p = 0.0006). In a lesion-based analysis, PCP showed a higher TBRmax than CP and NCP (1.17 ± 0.19 versus 1.00 ± 0.24 and 0.92 ± 0.18, respectively, p < 0.0001), and the lesions with high-risk features had a higher TBRmax than those without (1.20 ± 0.21 versus 1.02 ± 0.20, p = 0.0011). ConclusionsCoronary arterial 18F-NaF uptake is related to total plaque burden, coronary event history, and specific features of coronary atherosclerosis based on CT analysis. 18F-NaF PET/CT, in combination with cardiac CT, may provide a new molecular imaging approach to identify high-risk patients and coronary atherosclerotic lesions.

Monophasic Wilms tumor with multiple skeletal metastases in a young female: A case report and review of literature

Wilms tumor (nephroblastoma) is the most common renal tumor in children. It is uncommon in adolescent and skeletal metastasis at the time of presentation is even rare. The present case is a rare monophasic blastemal variant of Wilms tumor presenting with multiple skeletal metastases in a young female. We report a case of 23-year-old female presented with severe low backache and colicky right loin pain of 1 month and constant dull aching left upper arm pain of 20 days duration. Contrast-enhanced computed tomography (CECT) abdomen revealed heterogeneously enhancing soft tissue density mass with central nonenhancing areas arising from the upper pole of the right kidney. Whole body 18F-Sodium Fluoride (NaF) Positron emission tomography computed tomography (PET/CT) bone scintigraphy revealed multiple skeletal metastases. The patient underwent right radical nephrectomy and the tumor was confirmed as adult Wilms tumor by histopathology and immunohistochemistry. Skeletal metastasis may be the first presentation in a case of adolescent Wilms tumor, and this possibility should be considered when an adolescent patient presents with flank pain and a renal mass. The clinical course of adult Wilms tumor with blastemal component is very aggressive with high chances of recurrence and mortality.

Utility of 18F-fluorodeoxy glucose and 18F-sodium fluoride positron emission tomography/computed tomography in the diagnosis of medication-related osteonecrosis of the jaw: A preclinical study in a rat model.

The aim of this study was to determine the clinical utility of positron emission tomography/computed tomography (PET/CT) using 18F-FDG and 18F-NaF for the diagnosis of osteonecrosis of the jaw (ONJ), by observing characteristics in rat models treated with zoledronic acid (ZA) and/or dexamethasone (DX) followed by tooth extraction. A total of 48 rats were divided randomly into four groups: Group 1, rats treated with ZA and DX; Group 2, rats treated with ZA; Group 3, rats treated with DX; and Group 4, rats treated with vehicle as normal controls. They underwent examinations with both 18F-FDG and 18F-NaF PET/CT at 4 weeks prior to tooth extraction (baseline) and 4 weeks after tooth extraction. Rats were then sacrificed to evaluate the histological incidence and characteristics of ONJ. Histological and radiological characteristics of all groups were compared to assess the effects of medication and tooth extraction. Baseline PET/CT studies using 18F-FDG and 18F-NaF showed no difference in uptake among the groups. However, 18F-FDG PET/CT performed at 4 weeks after tooth extraction showed increased glucose metabolism at the extraction site in both the ZA/DX and the ZA-only groups compared with that in the vehicle-treated group, in accordance with the higher incidence of histological ONJ (p < 0.05, respectively). 18F-NaF PET/CT performed at 4 weeks after tooth extraction showed decreased bone uptake in the extraction site in the ZA/DX, ZA, and DX groups versus the vehicle group (all p < 0.05), but this was not correlated with the incidence of histological ONJ. The incidence of ONJ was highest in the ZA/DX group (66.7%), followed by the ZA group, both of which were significantly higher than in the DX and vehicle groups (both p < 0.05). 18F-FDG PET/CT as an inflammatory marker appeared to be a more appropriate imaging modality than 18F-NaF PET/CT in diagnosing ONJ in a rat model including a ZA/DX group. However, the decreased bone remodeling tendency highlighted by 18F-NaF PET/CT may be an indicator of a possible risk of ONJ before the onset of clinical signs and symptoms.

Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification.

18F-sodium fluoride positron emission tomography is a marker of vascular shear stress and aortic atherosclerosis

18F-sodium fluoride positron emission tomography is a marker of vascular shear stress and aortic atherosclerosis

Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography

Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography

Cabozantinib Resolves Bone Scans in Tumor-Naïve Mice Harboring Skeletal Injuries

The receptor tyrosine kinase inhibitor cabozantinib (XL184, BMS-907351 Cometriq) has displayed impressive clinical activity against several indications, culminating in its recent approval for medullary thyroid cancer. Among malignancies with tropism for the bone (prostate, breast), one striking feature of early clinical reports about this drug has been the rapid and complete resolution of bone scans, a phenomenon almost never observed even among therapies already shown to confer survival benefit. In castration-resistant prostate cancer, not all conventional response indicators change as dramatically posttreatment, raising the possibility that cabozantinib may impair the ability of bone-seeking radionuclides to integrate within the remodeling bone. To test this hypothesis, we surgically induced bone remodeling via physical insult in non-tumor-bearing mice and performed 18F-sodium fluoride (18F-NaF) positron emission tomographic (PET) and technetium 99m-methylene diphosphonate (99mTc-MDP) single-photon emission computed tomographic (SPECT) scans pre- and posttreatment with cabozantinib and related inhibitors. A consistent reduction in the accumulation of either radiotracer at the site of bone remodeling was observed in animals treated with cabozantinib. Given that cabozantinib is known to inhibit several receptor tyrosine kinases, we drugged animals with various permutations of more selective inhibitors to attempt to refine the molecular basis of bone scan resolution. Neither the vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib, the MET inhibitor crizotinib, nor the combination was capable of inhibiting 18F-NaF accumulation at known bioactive doses. In summary, although the mechanism by which cabozantinib suppresses radionuclide incorporation into foci undergoing bone remodeling remains unknown, that this phenomenon occurs in tumor-naïve models indicates that caution should be exercised in interpreting the clinical significance of this event.

Age-related differences in the activity of arterial mineral deposition and regional bone metabolism: a 18F-sodium fluoride positron emission tomography study

Functional (18)F-fluoride PET demonstrated an inverse relationship between the activity of arterial mineral deposition and regional bone metabolism. While bone metabolism decreases with age, the activity of arterial mineral deposition increases. The extent of arterial calcification increases with age, whereas bone mineral density decreases, evidencing a well-known inverse correlation on morphological basis. The aim of this study was to evaluate the functional relationship between the activity of arterial mineral deposition and regional bone metabolism as assessed by (18)F-sodium fluoride (NaF) PET/CT. Three hundred four subjects were examined by (18)F-NaF PET/CT. Tracer accumulation in the femoral arteries was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio). Uptake was compared with cardiovascular risk factors (RFs), calcified plaque burden, and regional bone metabolism as assessed by PET/CT. The activity of arterial mineral deposition significantly increased with age (p < 0.001), whereas regional bone metabolism significantly decreased (p < 0.001). There was a significant inverse correlation between bone metabolism and arterial mineral deposition (unadjusted, p < 0.001); that association was not significant (p = 0.79) when controlled for age and other RFs. Both high activity of arterial mineral deposition and low bone metabolism were significantly associated with cardiovascular events and other RFs. (18)F-NaF PET/CT provides a tool to visualize and quantify the activity of arterial mineral deposition and regional bone metabolism. In this study, we observed an inverse correlation between the activity of arterial mineral deposition and regional bone metabolism. While the activity of arterial mineral deposition significantly increases with age, regional bone metabolism decreases.

Association of linear 18F-sodium fluoride accumulation in femoral arteries as a measure of diffuse calcification with cardiovascular risk factors: A PET/CT study

BackgroundThe aim of this study was to correlate linear 18F-sodium fluoride accumulation in the femoral arteries as a measure of diffuse mineral deposition in medial elastocalcinosis with cardiovascular risk factors (RFs) and calcified plaque burden (CPB). Methods and ResultsIn this study, 409 patients were examined by 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT). Tracer accumulation was analyzed both qualitatively and semiquantitatively by measuring the target-to-background ratio, and compared with cardiovascular RFs and CPB. Linear 18F-sodium fluoride accumulation was observed in 159 (38.9%) patients and correlated significantly with age (P < .0001), hypertension (P < .0001), hypercholesterolemia (P = .0003), diabetes (P = .0003), history of smoking (P = .0007), prior cardiovascular events (P = .03), and CPB (P < .0001). The prevalence of linear tracer uptake increased as the number of cardiovascular RFs increased (P < .0001). ConclusionsLinear 18F-sodium fluoride uptake in the femoral arteries (1) provides a measure of diffuse mineral deposition, (2) demonstrates a highly significant correlation with cardiovascular RFs and CPB, and (3) is found to accumulate more frequently in patients with a high-risk profile for cardiovascular events. 18F-sodium fluoride PET/CT may become a unique tool for in vivo visualization and quantification of ongoing calcification in large arteries.