18F-sodium Fluoride Research Articles

Estimation of patient effective doses in PET/CT- 18F-Sodium Fluoride examinations

The positron emitters (18F-Sodium Fluoride (NaF)) and X-rays used in Positron emission tomography (PET) combined with computed tomography (PET/CT) imaging have a high radiation dose, which results in a high patient dose. The present research intends to determine the radiation dose and risks associated with PET/CT- 18F-Sodium fluoride examinations in patients. The 18F–NaF PET/CT was used to investigate the doses of 86 patients. Patient exposure parameters and ImPACT software were used to calculate mean effective doses. The administered activity of 185 MBq (5.0 mCi) per procedure has a mean and range based on the patient's BMI (BMI). The range of patient effective doses per procedure was found to be 4–10 mSv, with a radiation risk of 1 × 10−5 per procedure. Patient doses are determined by the patient's size, scanner type, imaging protocol, and reconstruction method. For further dose reduction, proper justification and radiation dose optimization is required.

18F-Sodium Fluoride (NaF) Uptake in Calcified Bladder Carcinoma: Double Density Sign

18F-Sodium fluoride (NaF) is primarily a skeletal imaging agent which can be localized in extraosseous calcified foci. Here, we describe a case of a 48-year-old man with bladder carcinoma referred for staging using 18F-NaF positron emission tomography/computed tomography (PET/CT). 18F-NaF PET/CT detected a calcified soft tissue mass in the urinary bladder. Extraosseous 18F-NaF uptake is often encountered and these non-osseous findings could possibly provide important diagnostic information. Thus, recognition of extraosseous 18F-NaF activity has implications for accurate staging and management.

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.

Temporal relationship between 18F-sodium fluoride uptake in the abdominal aorta and evolution of CT-verified vascular calcification

BackgroundFluoride-18 sodium fluoride (18F-NaF) localizes in microcalcifications in atheroma. The microcalcifications may aggregate, passing the resolution threshold to visualize on computed tomography (CT). We evaluated serial NaF positron emission tomography (PET)-CT scans to determine the temporal relationship between vascular NaF uptake and CT evident calcification in the abdominal aorta. MethodsProstate cancer patients who had at least 3 NaF PET-CT scans over at least 1.5 years were retrospectively enrolled. Regions of interest were traced in the abdominal aorta on both PET and CT images, excluding skeletal NaF activity. The maximum standardized uptake value (SUVmax) of NaF and the density and volume of calcium (exceeding 130 HU) were summed and divided by the number of slices to produce the SUVmax/slice and the mm3·slice−1 of calcium. ResultsOf 437 patients, 45 patients met criteria. NaF uptake waxed and waned between scans, while the calcium volume plateaued or increased over time. NaF uptake correlated with calcium volume on the baseline scan (P = .60, < .0001†) and calcium volume increment, especially from 1.0 to 1.5 years (r = .79, P < .0001†). Patients with persistently high NaF uptake showed a higher calcium volume increment (0-1.5 years) than patients with low or transiently high NaF uptake. ConclusionsAbdominal aortic NaF uptake varied over time. NaF uptake on the baseline scans and high NaF uptake on the serial scans preceded an increase in calcium volume, especially by 1.0-1.5 years. Persistently high NaF uptake was associated with a greater increment in calcium volume than patients with transiently elevated or persistently low fluoride uptake.

18F-sodium fluoride positron emission tomography (NaF-18-PET/CT) radiomic signatures to evaluate responses to alpha-particle Radium-223 dichloride therapy in osteosarcoma metastases

Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na18F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na18F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18F− -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18F− per 1 cm3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an “N of 1” case and warrants in depth analysis individually.

Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis

ObjectiveTo assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).MethodsWe performed 18F-sodium fluoride (18F-NaF)...

Lesion detection in 18F-sodium fluoride bone imaging: a comparison of attenuation-corrected versus nonattenuation-corrected PET reconstructions from modern PET-CT systems.

An earlier study demonstrated comparable lesion detection between attenuation-corrected (AC) and nonattenuation-corrected (NAC) 18F-sodium fluoride (NaF) PET images, which is relevant for computed tomography (CT) radiation dose-saving. However, this finding may not be applicable to newer systems. The aim was to compare lesion detection between AC and NAC NaF PET images on modern PET-CT systems. One expert and one nonexpert observer retrospectively surveyed NaF PET data in 25 breast cancer patients. At both lesion and patient level, each observer classified bone abnormalities as malignant, equivocal or benign, from NAC and AC PET images in the absence of CT. Expert interpretation of NaF PET-CT with the review of all diagnostic imaging/pathology reports for at least the subsequent 12 months provided reference standard metastases status at the patient level. Two-tailed Wilcoxon signed-rank tests measured statistically significant differences in total lesion detection between AC and NAC PET. Quadratic-weighted kappa score measured agreement in patient metastases status between observers. On a lesion-basis, AC PET images showed significantly more lesions than NAC for both the expert (122 versus 96; P = 0.002) and nonexpert (146 versus 132; P = 0.036) observers, with a large number of patients demonstrating disparity between AC and NAC images. For metastases status at the patient level without CT, NAC PET showed slightly better diagnostic accuracy than AC due to fewer false-positive results, as fewer lesions were identified. AC PET data provided superior lesion detection to NAC in NaF bone examinations and are thus required for clinical interpretation.

Update on imaging in chronic kidney disease-mineral and bone disorder: promising role of functional imaging.

Disorders of mineral metabolism and bone disease are common complications in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. Bone biopsies, bone scintigraphy, biochemical markers, and plain films have been used to assess bone disorders and bone turnover. Of these, functional imaging is less invasive than bone/marrow sampling, more specific than serum markers and is therefore ideally placed to assess total skeletal metabolism. 18F-sodium fluoride (NaF) PET/CT is an excellent bone-seeking agent superior to conventional bone scan in CKD patients due to its high bone uptake, rapid single-pass extraction, and minimal binding to serum proteins. Due to these properties, 18F-NaF can better assess the skeletal metabolism on primary diagnosis and following treatment in CKD patients. With the increased accessibility of PET scanners, it is likely that PET scanning with bone-specific tracers such as 18F-NaF will be used more regularly for clinical assessment and quantitation of bone kinetics. This article describes the pattern of scintigraphic/functional appearances secondary to musculoskeletal alterations that might occur in patients with CKD.

605P Analysis of serial PET imaging and paired Tc99 scans in metastatic castration resistant prostate cancer (mCRPC) treated with enzalutamide

Current and emerging PET platforms will enhance the ability to evaluate metastatic lesions in mCRPC. It remains unclear how the evolution of new lesions on more sensitive scans can improve clinical care as all current therapeutics were developed using CT Scan and Tc99m-MDP (Tc99) bone scans. 18F-Sodium Fluoride (NaF) PET imaging has increased sensitivity for bone lesions relative to Tc99. Here we test a semi-automated method of assessing NaF PET using a novel technology.

Alavi-Carlsen Calcification Score (ACCS): A Simple Measure of Global Cardiac Atherosclerosis Burden.

Multislice cardiac CT characterizes late stage macrocalcification in epicardial arteries as opposed to PET/CT, which mirrors early phase arterial wall changes in epicardial and transmural coronary arteries. With regard to tracer, there has been a shift from using mainly 18F-fluorodeoxyglucose (FDG), indicating inflammation, to applying predominantly 18F-sodium fluoride (NaF) due to its high affinity for arterial wall microcalcification and more consistent association with cardiovascular risk factors. To make NaF-PET/CT an indispensable adjunct to clinical assessment of cardiac atherosclerosis, the Alavi–Carlsen Calcification Score (ACCS) has been proposed. It constitutes a global assessment of cardiac atherosclerosis burden in the individual patient, supported by an artificial intelligence (AI)-based approach for fast observer-independent segmentation. Common measures for characterizing epicardial coronary atherosclerosis by NaF-PET/CT as the maximum standardized uptake value (SUV) or target-to-background ratio are more versatile, error prone, and less reproducible than the ACCS, which equals the average cardiac SUV. The AI-based approach ensures a quick and easy delineation of the entire heart in 3D to obtain the ACCS expressing ongoing global cardiac atherosclerosis, even before it gives rise to CT-detectable coronary calcification. The quantification of global cardiac atherosclerotic burden by the ACCS is suited for management triage and monitoring of disease progression with and without intervention.

Clinical implications of 18F-sodium fluoride uptake in subclinical aortic valve calcification: Its relation to coronary atherosclerosis and its predictive value

BackgroundUptake of 18F-sodium fluoride (18F-NaF) on positron emission tomography (PET) reflects active calcification. Application of this technique in the early phase of aortic valve calcification (AVC) is of clinical interest. We investigated clinical implications of 18F-NaF uptake in subclinical AVC evaluated simultaneously with coronary atherosclerosis, and the utility of 18F-NaF uptake in predicting AVC progression. MethodsWe studied 25 patients with subclinical AVC and coronary plaques detected on computed tomography (CT) who underwent 18F-NaF PET/CT. AVC score, volume, mean density, and the presence of high-risk coronary plaque were evaluated on CT in each patient. Focal 18F-NaF uptake in AVC and in coronary plaques was quantified with the maximum tissue-to-background ratio (TBRmax). ResultsThere were positive correlations between AVC TBRmax (A-TBRmax) and AVC parameters on CT. The 14 patients with high-risk coronary plaque had significantly higher A-TBRmax than those without such plaque (1.60 ± 0.18 vs 1.42 ± 0.13, respectively; P = 0.012). A-TBRmax positively correlated with maximum TBRmax of coronary plaque per patient (r = 0.55, P = 0.0043). In the 11 patients who underwent follow-up CT scan, A-TBRmax positively correlated with subsequent increase in AVC score (r = 0.74, P = 0.0091). ConclusionOur 18F-NaF PET- and CT-based data indicate relationships between calcification activity in subclinical AVC and characteristics of coronary atherosclerosis. 18F-NaF PET may provide new information regarding molecular conditions and future progression of subclinical AVC.

Lipids and cardiovascular calcification: contributions to plaque vulnerability.

Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability. Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models. The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.

18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications.

In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.

Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover. 18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a 18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche’s historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1–L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, 18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.

Atorvastatin Promotes Macrocalcification, But Not Microcalcification in Atherosclerotic Rabbits: An 18F-NaF PET/CT Study.

Our study aimed to investigate the effect of atorvastatin on plaque calcification by matching the results obtained by 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) with data from histologic sections. The rabbits were divided into 2 groups as follows: an atherosclerosis group (n = 10) and an atorvastatin group (n = 10). All rabbits underwent an abdominal aortic operation and were fed a high-fat diet to induce atherosclerosis. Plasma samples were used to analyze serum inflammation markers and blood lipid levels. 18F-NaF PET/CT scans were performed twice. The plaque area, macrophage number and calcification were measured, and the data from the pathological sections were matched with the 18F-NaF PET/CT scan results. The mean standardized uptake value (0.725 ± 0.126 vs. 0.603 ± 0.071, P < 0.001) and maximum standardized uptake value (1.024 ± 0.116 vs. 0.854 ± 0.091, P < 0.001) significantly increased in the atherosclerosis group, but only slightly increased in the atorvastatin group (0.616 ± 0.103 vs. 0.613 ± 0.094, P = 0.384; 0.853 ± 0.099 vs.0.837 ± 0.089, P < 0.001, respectively). The total calcium density was significantly increased in rabbits treated with atorvastatin compared with rabbits not treated with atorvastatin (1.64 ± 0.90 vs. 0.49 ± 0.35, P < 0.001), but the microcalcification level was significantly lower. There were more microcalcification deposits in the areas with increased radioactive uptake of 18F-NaF. Our study suggests that the anti-inflammatory activity of atorvastatin may promote macrocalcification but not microcalcification within atherosclerotic plaques. 18F-NaF PET/CT can detect plaque microcalcifications.

Two-year change in 18F-sodium fluoride uptake in major arteries of healthy subjects and angina pectoris patients.

To examine 2-year changes in carotid and aortic 18F-sodium fluoride (NaF) uptake in both healthy controls and angina pectoris patients. Twenty-nine healthy subjects and 20 angina pectoris patients underwent 90-min NaF-PET/CT twice 2 years apart. The carotids and three sections of the aorta (arch, thoracic, abdominal) were manually segmented. NaF uptake was expressed as the mean and total standardized uptake values without and with partial volume correction (SUVmean, SUVtotal and pvcSUVmean, pvcSUVtotal). Insignificant tendencies were higher NaF uptake in angina patients at both time points with less uptake in healthy subjects and higher uptake in angina patients after 2years. Thus, aortic pvcSUVmean of angina patients was 1.14 ± 0.35 and 1.29 ± 0.71 at baseline and after 2years vs. 0.99 ± 0.31 and 0.95 ± 0.28 in healthy subjects. A similar pattern was observed for the carotid pvcSUVmean. NaF uptake at baseline could not predict a change in CT-calcification after 2years. NaF uptake in all parts of the aorta correlated positively with age. There was an insignificant, but consistent, tendency for slightly higher arterial NaF uptake in the angina group indicating more ongoing microcalcification at both time points in patients than healthy subjects. The 2-year changes were in both groups very small suggesting that the atherosclerotic process is slow, albeit with a tendency of slight decreases among healthy controls and slight increases in angina patients despite statin therapy in half of these.

Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial.

Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Machine Learning with 18F-Sodium Fluoride PET and Quantitative Plaque Analysis on CT Angiography for the Future Risk of Myocardial Infarction.

Coronary 18F-sodium fluoride (18F-NaF) PET and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and 18F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40-59) months of follow-up. On univariable receiver-operator-curve analysis, only 18F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18F-NaF PET), we achieved a substantial improvement (P = 0.008 versus 18F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model.

Detecting native and bioprosthetic aortic valve disease using 18F-sodium fluoride: Clinical implications

Calcific aortic valve disease is the most common valvular disease and confers significant morbidity and mortality. There are currently no medical therapies that successfully halt or reverse the disease progression, making surgical replacement the only treatment currently available. The majority of patients will receive a bioprosthetic valve, which themselves are prone to degeneration and may also need replaced, adding to the already substantial healthcare burden of aortic stenosis. Echocardiography and computed tomography can identify late-stage manifestations of the disease process affecting native and bioprosthetic aortic valves but cannot detect or quantify early molecular changes. 18F-fluoride positron emission tomography, on the other hand, can non-invasively and sensitively assess disease activity in the valves. The current review outlines the pivotal role this novel molecular imaging technique has played in improving our understanding of native and bioprosthetic aortic valve disease, as well as providing insights into its feasibility as an important future research and clinical tool.

Effects of administration route on uptake kinetics of 18F-sodium fluoride positron emission tomography in mice

18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.