18F-NaF PET-CT Research Articles

Exploring the relationship between aortic valve microcalcification and cardiovascular risk factors with 18F-NaF PET-CT

Exploring the relationship between aortic valve microcalcification and cardiovascular risk factors with 18F-NaF PET-CT

Increased aortic valve uptake of sodium fluoride is associated with higher cardiovascular risk: assessing pathophysiology with PET/CT

Abstract Introduction Positron emission tomography-computed tomography (PET-CT) with 18F-sodium fluoride (18F-NaF) has been used in clinical research to characterize active microcalcification in aortic valve disease. However, its role in apparently healthy patients remains unknown. Purpose We aimed to characterize the aortic valve uptake of 18F-NaF in patients with high cardiovascular (CV) risk without known aortic valve disease. Methods Forty high CV-risk individuals without previous CV events or known aortic valve disease were scanned with 18F-NaF PET-CT. Aortic valve uptake of 18F-NaF was evaluated in 3-D multiplanar fusion images, considering top to bottom of the aortic valve for the establishment of circular regions of interest (ROI) around the valve. Maximum and mean standardized uptake values (SUV) estimated for each slice and the whole valve were corrected for blood-pool activity (mean of five ROI in the mid lumen of superior vena cava) by subtraction (corrected uptake per lesion, CUL) and division (tissue to background ratio, TBR). All patients underwent transthoracic echocardiography for aortic valve evaluation. Results The patients presented a mean age of 64.63 ± 8.87 years and 65% were males. The mean SCORE2 was 13.28 ± 8.48 and the mean ASCVD was 32.30 ± 20.55. Median CUL was 0.52, IQR 0.41-0.64, and median TBR was 1.62, IQR 1.47-1.75. The mean peak aortic valve velocity was 1.71 ± 0.41 m/s while the mean peak and mean gradients were 12.18 ± 5.47 mmHg and 6.50 ± 3.13 mmHg, respectively. Only 2 patients fulfilled the echocardiographic criteria for mild aortic stenosis. Patients were grouped according to the 50th percentile of both the ASCVD risk score and the SCORE2. Maximum SUV was associated with higher CV risk predicted by ASCVD risk score (1.60, IQR 1-30-2.10 vs 1.30, IQR 1.25-1.55; p<0.01) and SCORE2 (1.60, IQR 1.30-1.95 vs 1.30, IQR 1.15-1.65; p=0.02), but not mean SUV. After correction for blood-pool activity, higher CV risk was associated with increased CUL both for ASCVD risk score (0.59, IQR 0.52-0.92 vs 0.44, IQR 0.28-0.53; p<0.01) and SCORE2 (0.59, IQR 0.52-0.84 vs 0.43 0.27-0.53; p<0.01). Higher CV risk was also associated with increased TBR, both for ASCVD risk score (1.71, IQR 1.59-1.77 vs 1.51, IQR 1.25-1.66; p<0.01) and SCORE2 (1.70, IQR 1.59-1.77 vs 1.51, IQR 1.25-1.66; p<0.01). There were no significant correlations between echocardiographic variables and neither maximum SUV, mean SUV, CUL, nor TBR. Conclusion Increased aortic valve uptake of 18F-NaF is associated with higher CV risk predicted by ASCVD risk score and SCORE2. In this cohort without known aortic valve disease, there was no link between aortic valve uptake of 18F-NaF and echocardiographic variables. Further studies with larger populations must confirm these findings and evaluate the potential role of increased aortic valve uptake of 18F-NaF in predicting disease progression.

Intra-individual comparison of 18F-sodium fluoride PET–CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial

Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. Canadian Institutes of Health Research.

Vascular uptake on 18F-sodium fluoride positron emission tomography: precursor of vascular calcification?

BackgroundMicrocalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification. Methods and ResultsThe data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was .11–.13 (P < .001) higher compared to areas where no calcification developed. ConclusionThe activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher.

Phase 2 Study of Carfilzomib and Bone Metabolism in Patients with Relapsed Multiple Myeloma

Background: Carfilzomib is an epoxyketone proteasome inhibitor (PI) that binds selectively and irreversibly to the constitutive proteasome and immunoproteasome. In addition to its direct cytotoxicity, PIs possess bone anabolic effect, by facilitating osteoblast differentiation, which in turn, inhibits multiple myeloma (MM) growth. However, the relative contribution of carfilzomib on direct tumor killing and bone formation has been difficult to discern when it is used in combination with other agents such as steroids, chemotherapeutics, or immunomodulatory agents (iMiDs); most of which increase bone loss.Objective: We explored the effect of single agent carfilzomib on bone metabolism and disease response in patients with relapsed MM.Methods: We conducted a phase II study of single-agent carfilzomib at 56 mg/m2 day 1, 2, 8, 9, 15, 16 of a 28 day cycle in patients with relapsed MM. Serum markers of bone resorption including carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and tartrate resistant acid phosphatase 5b (TRACP 5b) and bone formation markers including N-terminal type 1 procollagen (P1NP) and osteocalcin (OC) were analyzed at baseline and 6 months after therapy, and compared using paired t-tests. Imaging using 18F-NaF PET-CT scans to monitor bone response and 8F-FDG PET-CT to measure localized tumor burden were done at baseline and 6 months post treatment. For each patient, the three sites with the highest baseline SUVs and an iliac crest (representing an uninvolved site) were selected for quantitative comparisons using paired t-test.Results: Ten patient were accrued. Average age was 70.1 +/- 6.79 (mean +/- SD) years. Median prior lines of therapy was 2. 9 were evaluable for response. Overall response rate was 77.8%: VGPR (1/9: 11%), partial response (6/9: 67%), stable disease (2/9: 22%). Median PFS was 11.5 months. Overall survival was 21.9 months. Common treatment adverse events (AE) were comparable to previous reports including diarrhea (40%), fever (40%), dyspnea (30%) and fatigue (30%). Grade 3/4 AEs, occurring in 10% each included neutropenia, thrombocytopenia, dyspnea, fatigue, vomiting, ataxia, heart failure and pulmonary edema.Serum ICTP and TRACP were elevated at baseline in 80% of subjects; means (+/- SD) of serum ICTP (14.4 +/- 3.1 ug/L) and TRACP (8.2 +/- 4.2 U/L), respectively. Both markers declined significantly after therapy (means +/- SD of serum ICTP 8.4 +/- 3.1 ug/L and TRACP (5.2 +/- 4.2 U/L); p<0.01), suggesting osteoclast suppression. Serum PINP and OC varied among subjects; 5 patients with low levels and 4 normal levels and 1 with elevated level: mean (+/- SD) of PINP 25 +/- 23 ug/L and OC (18 +/- 12 ug/L). Neither post treatment mean PINP nor OC differed significantly from baseline overall (p=0.16). However, all subjects who achieve PR or better had a more than 25% increase in PINP and OC, suggesting increased new bone formation.8F-FDG and 18F-NaF were positive in all subjects. Number of active sites and SUVs vary largely among subjects. 18F-NaF images mirrored the 8F-FDG signals, appearing as rings around the tumor sites, suggesting a bone reaction to the localized tumors. 6 of 9 subjects had post treatment PET/CTs for paired comparison. Post treatment 8F-FDG SUV of representative sites decreased significantly, while 18F-NaF SUVs varied; 58% of lesions had a decline in SUV, while 32% were unchanged and 10% were brighter, suggesting heterogeneous bone response. 18F-NaF SUVs of iliac sites decreased post treatment, suggesting a lower bone turnover overall. CT scans showed increased sclerosis at the rim of lytic lesions without significant change in lesion size, at this early time point.Conclusion: Carfilzomib at 56 mg/m2 dosing strongly inhibits bone resorption and demonstrates bone anabolic effects, in addition to cytotoxicity, in relapsed MM. Single agent use allows bone response analysis without the confounding effects of other anti-MM agents used in combination therapy. Response rates and side effects are favorable to prior reports. Serum markers of bone remodeling are useful for an assessment of overall bone metabolism while the 18F-NaF PET/CT allows assessment of both local and systemic changes but lacks specificity. Studies of osteoblast differentiation from subject's bone marrow stromal cells pre and post treatment are ongoing. Whether carfilzomib can heal bone lesions requires longer follow up. DisclosuresSuvannasankha:Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Janssen Pharmaceuticals: Research Funding. Abonour:Celgene: Other: Steering committee, Research Funding; Prothena: Research Funding; Takeda: Other: Steering committee, Research Funding. Roodman:PharmaMar: Research Funding.

The ability of Micropure® ultrasound technique to identify microcalcifications in carotid plaques

ObjectivesTo study the ability of Micropure® ultrasound technique to identify microcalcifications in carotid plaques. MethodsForty-four carotids in 22 patients were enrolled in this study and were detected by routine ultrasound examination and Micropure® examination at the same time to identify microcalcifications in plaques. The results were compared with the tissue-background ratio (TBR) in 18F-NaF PET-CT imaging, which was performed one or two days after the ultrasound examination. ResultsIn the 44 carotids, plaques were detected in 37 carotids. Microcalcifications were detected by the Micropure® technique in 32 carotids, which were located surrounded by macrocalcifications in 23 carotids, in the fibre cap in 12 carotids, and in the base of the plaque in 6 carotids. Microcalcifications were not detected in 12 carotids. In 18F-NaF PET-CT examination, TBR > 1.61 (range 1.62–3.99, mean 2.25 ± 0.58) was detected in 37 carotids, and TBR < 1.61 was detected in 7 carotids. There were no significant differences between the two methods in detecting microcalcifications (p = 0.180). The sensitivity of the Micropure® technique in detecting microcalcifications was 81.08 %, and the specificity was 71.43 %. ConclusionsMicrocalcifications in the carotid artery detected by the Micropure® technique were well in accordance with 18F-NaF PET-CT scanning, with better sensitivity and specificity.

The Impact of 18F-DCFPyL PET-CT Imaging on Initial Staging, Radiation, and Systemic Therapy Treatment Recommendations for Veterans With Aggressive Prostate Cancer

PurposeOur purpose was to study the effect of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) positron emission tomography (PET)-computed tomography (CT) on staging/treatment recommendations of previously untreated prostate cancer. We report here results of a prospective single center single arm imaging trial within Veterans Affairs (Greater Los Angeles): the frequency of patients upstaged to M1 disease (primary endpoint) and the frequency of patients with change in treatment recommendations (secondary endpoint). This is the first report of prostate-specific membrane antigen PET-CT exclusive to U.S. veterans. Methods and MaterialsVeterans with Gleason ≥4 + 3, clinical stage ≥T2c, or prostate-specific antigen >10 ng/mL were eligible. Patients underwent conventional imaging (99mTc-methyl diphosphonate bone scan or 18F-NaF PET-CT; and pelvic CT or pelvic magnetic resonance imaging) in addition to 18F-DCFPyL PET-CT. The effect of 18F-DCFPyL PET-CT on treatment change was determined by applying prespecified treatment recommendations based on National Comprehensive Cancer Network guidelines and modern clinical practice. ResultsOne hundred patients underwent 18F-DCFPyL PET-CT. Nineteen out of 84 (23%) patients initially thought to be nonmetastatic were upstaged to M1; 8/16 (50%) patients initially thought to have M1 disease were downstaged to M0. In total, 39/100 (39%) had a change in prespecified treatment recommendations, including change of radiation therapy volume/dose in 39/100 (39%) and starting abiraterone in 22/100 (22%). ConclusionsIncorporation of 18F-DCFPyL PET-CT into the initial conventional imaging workup for prostate cancer can substantially affect staging/treatment recommendations.

Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden.

18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. In 50 patients (64% males, 63 ± 7years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Relationship between lower lumbar spine shape and patient bone metabolic activity as characterised by 18F NaF bio-markers

Chronic lower lumbar pain has been associated with elevated bone metabolic activity in the spine. Diagnosis of bone metabolic activity is currently through integrating Positron Emission Tomography (PET) with Sodium Fluoride (18F–NaF) biomarkers. It has been reported that numerous observable pathologies including lumbar fusion, disc abnormalities and scoliosis have often been associated with increased 18F–NaF uptake. The aim of this study was to identify what features of lower lumbar shape most strongly correlate with 18F–NaF uptake. Following a principal component analysis of 23 patients who presented with lumbar pain and underwent 18F–NaF PET-CT, it was revealed that three modes interpreted as (i) sacral tilt, (ii) vertebral disc spacing and (iii) spine size were the three characteristics that described 88.7% of spine shape in our study population. 18F–NaF was described by two modes including 18F–NaF intensity and spatial variation (anterior-inferior to posterior-superior). 18F–NaF was most sensitive to sacral tilt followed by vertebral disc spacing. A predictive model derived from that spine population was able to predict 18F–NaF ‘hot-spot’ locations with 85 ± 5% accuracy and with 71 ± 3% accuracy for the 18F–NaF magnitude. These results suggest that patients reporting with lower lumbar pain and who present with increased sacral tilt profiles and/or reduced disc spacing are good candidates for further 18F–NaF PET-CT imaging, evidenced by the high association between those shape profiles and 18F–NaF uptake.

Quantitative in vivo assessment of bone allograft viability using 18F-fluoride PET/CT after glenoid augmentation in reverse shoulder arthroplasty: a pilot study.

Success after glenoid bone augmentation in total shoulder arthroplasty depends on osseous integration and non-resorption. Standard imaging techniques, such as computed tomography (CT) and X-rays, cannot quantify bone viability. Therefore, we introduce a new technique to assess graft viability using 18F-sodium fluoride (18F-NaF) PET-CT for femoral allografts in reverse total shoulder arthroplasty (RSA). Patient charts were reviewed following glenoid augmentation using femoral allografts in reverse total shoulder arthroplasty. A total of seven patients were included in this study. 18F-NaF PET-CT was used to assess graft viability and graft fusion. Semiquantitative assessment of 18F-NaF uptake was performed by means of a standardized uptake value (SUV). Radiographs were used to assess fusion. The mean age of the patients at the time of follow-up was 83.4years (range 79-92), and the mean follow-up was 44.4months. Viability and fusion were confirmed in all allografts using semiquantitative analysis of 18F-NaF PET-CT by means of standardized uptake value (SUVmax). Metabolic activity of medullary region of a vertebral spine was defined as a reference background. The mean value of maximum tracer activity in the allograft was not statistically different from native bone in the reference vertebrae (p = 0.14). 18F-NaF PET-CT is a practicable tool to quantitatively assess viability in large bone allografts after glenoid augmentation in RSA. The study shows viability and fusion in all allografts. Level IV, treatment study.

18F-FLOURIDE POSITRON EMISSION TOMOGRAPHY MAGNETIC RESONANCE VERSUS POSITRON EMISSION TOMOGRAPHY COMPUTERISED TOMOGRAPHY IN VALVULAR AND CORONARY HEART DISEASE: A COMPARISON OF ATTENUATION CORRECTION METHODS

18F-NaF PET CT can image aortic valve and coronary artery microcalcification. With reduced radiation exposure PET MR may be favoured over PET CT but concern remains over the accuracy of attenuation correction (AC) maps. We compared 18F-NaF uptake across PET CT and PET MR using breath held, free

Technical feasibility, radiation dosimetry and clinical use of 18F-sodium fluoride (NaF) in evaluation of metastatic bone disease in pediatric population.

The role of 18F-fluoride (18F-NaF) PET-CT for the detection of bone metastases in adults is well established and is considered superior to conventional bone scintigraphy. However, data pertaining use of 18F-NaF PET-CT in pediatric oncology is relatively sparse. The aim of the present study is to retrospectively analyze and share a single-center experience of 18F-NaF PET-CT in pediatric population and to provide preliminary information regarding imaging technique, feasibility of this modality in young patients and radiation dosimetry measurements in pediatric oncology cases. Twenty-four pediatric patients (mean age 8.0 ± 3.9) were included in the study for retrospective analysis. All patients were referred for primary staging or restaging for potential osseous metastatic disease and PET-CT scan was performed by injecting 2.2MBq/kg (0.06mCi/kg) of 18F-NaF. Nine patients were imaged for primary staging and in all cases increase osteoblastic activity was seen in the primary tumor and of these, metastatic bone disease was identified in 2/9 patients. In the restaging group comprising 15/24 patients, metastatic deposits were identified in 3/15 whilst no disease was seen in the remaining 12 patients. Patients were injected a mean dose of 90.35 ± 22.9MBq with an estimated mean effective absorbed doses of 2.98 ± 0.75mSv for 18F-NaF and 3.37 ± 2.4mSv for CT alone. Mean cumulative effective dose of 18F-NaF PET-CT scan was 5.11 ± 2.7mSv. 18F-NaF PET-CT may be a feasible alternative to 99mTc MDP for radionuclide bone scintigraphy in the evaluation of pediatric bone pathology. Due to its better pharmacokinetics, there is potential that osseous staging can be achieved with relatively low doses and with a similar radiation burden as with 99mTc-MDP imaging.

18F–Sodium Fluoride Uptake in Abdominal Aortic Aneurysms: The SoFIA3 Study

BackgroundFluorine-18–sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque. ObjectivesIn patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes. MethodsIn prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter <30 mm) underwent abdominal ultrasound, 18F-NaF PET-CT, CT angiography, and calcium scoring. Clinical endpoints were aneurysm expansion and the composite of AAA repair or rupture. ResultsFluorine-18-NaF uptake was increased in AAA compared with nonaneurysmal regions within the same aorta (p = 0.004) and aortas of control subjects (p = 0.023). Histology and micro-PET-CT demonstrated that 18F-NaF uptake localized to areas of aneurysm disease and active calcification. In 72 patients within the longitudinal cohort study (mean age 73 ± 7 years, 85% men, baseline aneurysm diameter 48.8 ± 7.7 mm), there were 19 aneurysm repairs (26.4%) and 3 ruptures (4.2%) after 510 ± 196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile (3.10 [interquartile range (IQR): 2.34 to 5.92 mm/year] vs. 1.24 [IQR: 0.52 to 2.92 mm/year]; p = 0.008) and were nearly 3× as likely to experience AAA repair or rupture (15.3% vs. 5.6%; log-rank p = 0.043). ConclusionsFluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events. (Sodium Fluoride Imaging of Abdominal Aortic Aneurysms [SoFIA3]; NCT02229006; Magnetic Resonance Imaging [MRI] for Abdominal Aortic Aneurysms to Predict Rupture or Surgery: The MA3RS Trial; ISRCTN76413758)

Atypical Hemangioma Mimicking Metastasis on 18F-Sodium Fluoride Positron Emission Tomography-Computed Tomography and Magnetic Resonance Imaging: Gallium-68-Prostate-Specific Membrane Antigen Positron Emission Tomography Improves the Specificity of Bone Lesions.

Vertebral hemangioma is a benign condition, but sometimes, it might represent as diagnostic dilemma especially in elderly patient mimicking serious pathology like metastasis. We report a case of a 66-year-old man with prostate cancer. 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) demonstrates increased radiotracer uptake at body of D4 vertebra. Magnetic resonance imaging shows features of atypical hemangioma; however, metastasis cannot be ruled out. To rule out bone metastasis, gallium-68-prostate-specific membrane antigen PET-CT is performed which shows no abnormal lesion. Eight-month follow-up by 18F-NaF PET-CT showed persistent osteoblastic lesion at D4 without any significant change thus, confirming the initial diagnosis of atypical hemangioma.

Novel weight-based dose threshold for 18F-NaF PET-CT imaging using advanced PET-CT systems: a potential tool for reducing radiation burden.

Fluorine-18-sodium fluoride (F-NaF) PET/CT is an important tool for detecting and evaluating metastatic bone cancer. Besides traditional dose metrics, recent methods such as real-time dose mapping, dose calculation from DICOM information, and their relevance to entrance skin exposure are currently in use to reduce the radiation burden. In this study, we have analyzed the data of 1062 patients retrospectively to evaluate patterns of absorbed dose for institutional weight-based dose protocol as compared with fixed dose method guidelines of Society of Nuclear Medicine and Molecular Imaging (SNMMI). The effective dose imparted by F-NaF (internal exposure) was calculated by using coefficient 0.089 mrem/mCi (0.024 mSv/MBq) according to ICRP publication 106. To estimate the effective dose from whole-body CT scan (external exposure), volume CT dose index (mGy) and dose length product (mGy cm) were directly obtained from the display screen of CT workstation. Effective dose was calculated by multiplying DLP (mGy cm) with ICRP conversion coefficient 'k' 0.015 (mSv/mGy cm). Of the total 1062 patients, there were metastases in 44% (464), probable malignancy in 9% (96), negative findings in 40.5% (433), equivocal findings in 3% (32), and probable benignancy in 3.5% (37). All patients were injected with an institutional agreed protocol of 2.22 MBq/kg (0.06 mCi/kg). The mean injected activity for entire population came out to be 4.79±0.99 mCi. The mean effective absorbed doses were 3.37±0.70 and 5.5±1.35 mSv for F-NaF alone and CT alone, respectively. The mean cumulative effective dose of combined F-NaF PET and CT scan was calculated to be 8.8±1.8 mSv. The minimum absorbed dose for our method was as follows: 1.37 mSv for Kuwait Cancer Control Center vs. 4.44 mSv for SNMMI. Absorbed dose for maximum injected activity was as follows: 5.7 mSv for Kuwait Cancer Control Center vs. 8.88 mSv for SNMMI. Our weight-based doses were also lower when compared with minimum and maximum absorbed doses of technetium-99m-methylene diphosphonate as per SNMMI guidelines (i.e. 4.21 and 6.32 mSv, respectively). Our weight-based dose protocol showed a significant reduction in absorbed doses (i.e. 69.14% for F-NaF and 67.45% for technetium-99m-methylene diphosphonate) when compared with fixed dose method guidelines of SNMMI. It is suggested that further prospective studies may be performed in adult population, to evaluate dosimetry efficacy of F-NaF at a low dose of 0.06 mCi/kg as inferred in our current 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.

Demons versus Level-Set motion registration for coronary 18F-sodium fluoride PET.

Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically plausible. Therefore, level-set technique will likely require additional post-processing steps. On the other hand, the observed TBR increases were the highest for the level-set technique. Further investigations of the optimal registration technique of this novel coronary PET imaging technique are warranted.

The Promising Role of Dynamic 18F-NaF PET-CT in Diagnosing Symptomatic Joint Prosthesis

Our purpose was to establish proof of principle case study for the use of dynamic 18F-NaF PET-CT in the assessment of knee and hip prostheses. Approval was granted by the research ethics committee and informed&lt;br /&gt;consent was obtained. This is a case study investigating the role of dynamic 18F NaF PET-CT in a patient with ilateral knee prostheses (1 symptomatic/painful and 1 asymptomatic). Both knees were studied with dynamic 18F-NaF PET-CT technique to demonstrate the different pattern of uptake in normal/asymptomatic joint as well as painful joints with aseptic loosening. In addition, a knee aspirate was obtained from the symptomatic knee and serum C-reactive protein and erythrocyte sediment rate levels as well as a peripheral white cell count were&lt;br /&gt;obtained in addition to 12 month clinical follow up. Images were obtained with multi-sequential dynamic image acquisition in list mode using GE Healthcare® volume imaging protocol (ViP) after an intravenous injection of 250 MBq 18F-NaF. The images were interpreted as normal, loosening or septic loosening based on the graphical pattern of tracer uptake produced at the bone-prosthesis interface. A final diagnosis was made by a combination of joint aspiration microbiology and clinical follow-up for 1 year; in addition to C-reactive protein and erythrocyte sediment rate levels as well as peripheral white cell count. NaF PET results were compared with 3-phase dynamic bone scan results and plain radiographs. The degree of uptake in the symptomatic joint exceeded background&lt;br /&gt;levels and also levels of uptake in the asymptomatic knee. The pattern of uptake and curve slope in both the asymptomatic and symptomatic joints matched the pattern of uptake in our hypothesis. Dynamic 18F-NaF PET-CT is a useful imaging modality for assessing painful joint prosthesis. It can differentiate between asymptomatic joints and aseptic loosening. However, more work is required for the detection of septic loosening.

Review of the role of dynamic 18F-NaF PET in diagnosing and distinguishing between septic and aseptic loosening in hip prosthesis

Joint replacements may fail due to infection, dislocation, peri-prosthetic fracture and loosening. Between 0.4 and 4% of joint replacements are known to be complicated by infection and aseptic loosening 2–18%. Differentiating between infection and aseptic loosening has an important bearing on the ongoing strategy for antimicrobial therapy and surgical intervention, but distinguishing one from the other can be difficult and will often require a battery of clinical and biochemical tests including the use of varying radiological modalities to accurately identify whether problematic joints are infected or aseptically loose. Prompt diagnosis is important due to the development of a biofilm on the surface of the infected prosthesis, which makes treatment difficult. There is no consensus among experts on the ideal imaging technique nor the methodology for image interpretation, but there is an increasing trend to apply hybrid imaging in the investigation of painful joint prosthesis and recent attempts have been made using PET-CT to identify aseptic loosening and infection with 18F-fluorodeoxyglucose (FDG) and sodium fluoride 18F-Na. The aim of this paper is to evaluate the role of 18F-NaF sodium fluoride (18F-NaF) positron emission tomography (PET) in distinguishing between septic and aseptic failure in hip and knee replacements, in addition to evaluating the feasibility of using multi-sequential 18F-NaF PET-CT for the assessment of painful lower limb prostheses.

¹⁸F-NaF PET-CT: a new method for imaging of ruptured and rupture-endangered atherosclerotic plaques

¹⁸F-NaF PET-CT: a new method for imaging of ruptured and rupture-endangered atherosclerotic plaques