Sodium Fluoride Positron Emission Tomography Research Articles

Comparison of PET/CT versus CT only in the assessment of new heterotopic ossification bone lesions in patients with fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder characterized by the deposition of bone in soft tissues, known as heterotopic ossification (HO). This post hoc analysis compared the performance of two imaging modalities for the detection and volumetric measurement of new HO lesions. LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP. From baseline through to week 28, 18F-labeled sodium fluoride positron emission tomography (PET)/X-ray computed tomography (CT) and CT-only scans prospectively acquired during the initial placebo-controlled period of the study were independently reviewed by two sets of fixed blinded readers plus an adjudicator for the presence and volume of new HO lesions. The number of patients with new lesions was 14/44 (31.8 %) and 12/44 (27.3 %) as detected by PET/CT and CT only, respectively. The aggregate number/volume of new lesions were very similar both for the placebo and the garetosmab group between PET/CT (27/245.0 cm3 and 3/21.3 cm3, respectively) and CT only (37/261.8 cm3 and 1/0.1 cm3, respectively). The mean (standard deviation) number of new lesions per patient by PET/CT through week 28 was 0.68 (1.57) versus 0.86 (1.95) as detected by CT only. Through week 28, the mean (standard deviation) volume of new lesions per patient detected by PET/CT was 6.05 (14.88) cm3 versus 5.94 (21.13) cm3 by CT only. Moderate agreement between PET/CT and CT-only detection was observed when identifying patients with new lesions, with a kappa coefficient of 0.46 (standard error, 0.146; 95 % confidence interval, 0.17–0.74). CT-only imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions. CT-only imaging therefore is a viable option for the assessment of therapies on new HO in patients with FOP.

Fluorine F 18 Sodium-Fluoride Positron Emission Tomography to Study Renal Osteodystrophy and Aortic Microcalcification in Patients with CKD: A Pilot Study

Fluorine F 18 Sodium-Fluoride Positron Emission Tomography to Study Renal Osteodystrophy and Aortic Microcalcification in Patients with CKD: A Pilot Study

Metabolic bone imaging and its relationship with biomechanics

ObjectiveThis mini review delves into the mechanisms of [18F]Sodium Fluoride positron emission tomography ([18F]NaF PET), which, by interrogating areas of newly mineralizing bone, provides a valuable tool to study the joint response to loading and areas of altered whole-joint function in osteoarthritis (OA). DesignThe review consolidates and discusses findings from both preclinical and clinical studies that utilize [18F]NaF PET to evaluate the bone response to various loading paradigms. It also briefly reviews technical considerations for PET imaging and discusses its strong potential as a tool in the quest to understand bone metabolism in the context of loading and osteoarthritis. ResultsWhile considering previous studies, technical considerations and potential new applications of this methodology are also discussed. [18F]NaF PET/MRI reveals localized, load-related bone responses after exercise, providing insights into early OA progression. In human studies, significant increases in tracer uptake are observed in areas affected by OA pathology, driven by bone perfusion and blood volume. Future work to examine the relationship between metabolic bone response to exercise and the bone loading environment is needed. ConclusionsIntegrating [18F]NaF PET/MRI with advanced biomechanical modeling holds promise for guiding clinical management of OA, primarily by examining the relationship between bone, soft tissues of the joint, and loading forces.

THU402 New Heterotopic Ossification Lesions In Patients With Fibrodysplasia Ossificans Progressiva Measured By PET/CT vs CT Only

Abstract Disclosure: D. Gonzalez Trotter: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. J. McGinniss: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A.N. Economides: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. K. Mohammadi: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A.J. Rankin: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Musser: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Mellis: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. E. Forleo-Neto: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. G. Herman: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder caused by mutations in the activin-A receptor type 1 (ACVR1) gene that render it responsive to activin-A, a ligand that normally antagonizes signaling from ACVR1. FOP is characterized by the deposition of bone in soft tissues known as heterotopic ossification (HO) and episodic painful flare-ups. Garetosmab, a fully human monoclonal antibody against activin-A, is being investigated for the prevention of new HO lesions in patients with FOP. This post hoc analysis compared the change from baseline in the number and volume of new HO lesions identified by 18F-labeled sodium fluoride (a bone-seeking tracer that measures bone deposition and turnover) positron emission tomography (PET/CT) and X-ray computed tomography (CT) imaging (which measures bone volume). Methods: Baseline and 28-week PET/CT and CT-only scans acquired during the initial double-blind placebo-controlled period of the LUMINA-1 (NCT03188666) phase 2 study were independently read by two sets of blinded readers and an adjudicator for the presence and volume of new lesions. Number and volume of new lesions were compared between the two imaging modalities. Results: The number of patients with new lesions as detected by PET/CT and CT only was 14/44 (31.8%) and 12/44 (27.3%), respectively. The mean number (standard deviation) of new lesions per patient by PET/CT through Week 28 was 0.68 (1.57) vs 0.86 (1.95) as detected by CT only. In patients with new lesions, the mean number of new lesions per patient was 2.14 (2.18) vs 3.17 (2.62) as detected by PET/CT vs CT only, respectively. The mean volume (cm3) of new lesions per patient detected by PET/CT was 6.05 (14.88) vs 5.94 (21.13) by CT only, through Week 28. In the subset of patients with new lesions, the mean volume of new lesions per patient detected by PET/CT was 19.02 (21.60) vs 21.79 (36.98) by CT only. Moderate agreement between PET/CT and CT-only detection was observed when identifying patients with new lesions, with a kappa coefficient of 0.46 (standard error: 0.146; 95% confidence interval: 0.17, 0.74). Placebo vs garetosmab groups, respectively, showed aggregate new lesion number/volume (cm3) of 27/245.0 vs 3/21.3 by PET/CT, and 37/261.5 vs 1/0.05 by CT only. Conclusions: CT imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions and provides a viable option for the assessment of therapies that may inhibit the formation of new HO lesions in patients with FOP. Presentation: Thursday, June 15, 2023

18F]sodium fluoride positron emission tomography: a systematic bibliometric review from 2008 to 2022.

As a noninvasive diagnostic tool, fluorine-18-labelled sodium fluoride positron emission tomography ([18F]NaF PET) has been increasingly applied in clinical practice due to its excellent imaging performance, attracting more attention from clinical practitioners. However, with the continuous development of technology and growth of knowledge, the field of [18F]NaF PET is changing. Nevertheless, few studies have conducted quantitative analyses of the literature in this field. Therefore, in this study, we used bibliometric methods to analyze the trends, content distribution, and frontiers of this field from multiple perspectives, including social and international structure, conceptual structure, and intellectual structure. This study used the Web of Science (WOS) core database as the data source and retrieved literature related to [18F]NaF PET between 2008 and 2022. CiteSpace and VOSviewer software were then employed for bibliometric analysis. This study performed co-occurrence analysis and citation analysis to investigate the characteristics of [18F]NaF PET in 3 aspects. A total of 682 articles related to [18F]NaF PET were collected during the period from 2008 to 2022. The author, Alavi, had the highest number of publications (67 articles). In terms of institutions, the University of Edinburgh had the highest number of publications (64 articles). The United States (300 articles) was the country with the highest number of published articles. Keyword co-occurrence analysis revealed that [18F]NaF PET-related technologies, bone metastasis (prostate cancer and breast cancer), and atherosclerosis were prominent research directions in this field. In terms of highly cited authors, Even-Sapir had the highest citation count (188 citations). Regarding highly cited journals, the Journal of Nuclear Medicine ranked as the most highly cited journal. The literature co-citation clustering and timeline graph showed that atherosclerotic plaques, bone metastasis, and the clinical applications of [18F]NaF PET were topics of active research in this field. There has been an increase in the literature published in the field of [18F]NaF PET from 2008 to 2022. The United States holds a prominent position in the field of [18F]NaF PET. Arteriosclerosis and bone metastasis are the main topics in this field and at the forefront of research.

Input function and modeling for determining bone metabolic flux using [18 F] sodium fluoride PET imaging: A step-by-step guide.

Studies of skeletal metabolism using measurements of bone metabolic flux (Ki ) obtained with [18 F] sodium fluoride ([18 F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating other metabolic bone diseases, including chronic kidney disease mineral and bone disorder. It has also been shown to be valuable in metastatic bone disease in breast cancer patients and may have potential in other cancer types, such as prostate cancer, to assess early bone fracture risk. However, these studies have usually required a 60-min dynamic PET scan and measurement of the arterial input function (AIF), making them difficult to translate into the clinic for diagnostic purposes. We have previously proposed a simplified method that estimates the Ki value at an imaging site from a short (4-min) static scan and venous blood samples. A key advantage of this method is that, by acquiring a series of static scans, values of Ki can be quickly measured at multiple sites using a single injection of the tracer. To date, the widespread use of [18 F]NaF PET has been limited by the need to measure the AIF required for the mathematical modeling of tracer kinetics to derive Ki and other kinetic parameters. In this report, we review different methods of measuring the AIF, including direct arterial sampling, the use of a semi-population input function (SP-AIF), and image-derived input function, the latter two requiring only two or three venous blood samples obtained between 30 and 60min after injection. We provide an SP-AIF model and a spreadsheet for calculating Ki values using the static scan method that others can use to study bone metabolism in metabolic and metastatic bone diseases without requiring invasive arterial blood sampling. The method shortens scan times, simplifies procedures, and reduces the cost of multicenter trials without losing accuracy or precision.

Quantitative 99mTc-MDP SPECT/CT as an alternative to 18F-NaF PET/CT for objective assessment of osteoblastic bone metastases.

To investigate the correlation between the standardized uptake value (SUV) metrics derived from technetium-99m (99mTc) methylene diphosphonate (MDP) single photon emission computed tomography/computed tomography (SPECT/CT) and fluorine-18 (18F) sodium fluoride (NaF) positron emission tomography (PET)/CT. A total of 129 metastatic lesions from 14 patients who underwent both 99mTc-MDP SPECT/CT and 18F-NaF PET/CT within one month were included in the analyses. The lesions with markedly increased uptake were semi-automatically segmented into a volume of interest in both SPECT and PET images by taking the 42% of maximum uptake as a threshold. Maximum, average and minimum SUV (namely, SUVmax, SUVmean and SUVmin) were recorded for each lesion. The strength of correlation was evaluated with Pearson's correlation analysis. The correlation coefficitients for SUVmax, SUVmean and SUVmin derived SPECT and PET images were 0.652, 0.653 and 0.635, respectively (all P<0.001). Lesions with a volume of at least 5cm3 demonstrated a stronger correlation, increasing the correlation coefficients to 0.714, 0.724 and 0.686, respectively (all P<0.001). The strongest correlation was seen in the lesions of the appendicular skeleton, with coefficients for SUVmax, SUVmean and SUVmin being 0.769, 0.791 and 0.761, respectively (all P<0.001). The SUV metrics derived from 99mTc-MDP SPECT/CT strongly correlate with 18F-NaF PET, especially for relatively large lesions located in the appendicular skeleton. Technetium-99m-MDP SPECT/CT could potentially be used as an alternative method to 18F-NaF PET/CT for quantitative evaluation and objective follow-up of bone metastases.

Abstract 13144: 18 F-NaF Positron Emission Tomography Imaging Detects Femoral Artery Microcalcification in Patients With Type 2 Diabetes Mellitus and Macroalbuminuria. An Early Marker for Vascular Disease?

Background: Although albuminuria is an established risk factor for progression of kidney disease and cardiovascular outcomes, its association with subclinical arterial disease is unclear. [ 18 F]-sodium fluoride ([ 18 F]NaF) positron emission tomography (PET) imaging allows detailed early visualization of arterial microcalcification. This study aims to compare non-invasive imaging markers of subclinical arterial disease measured by microcalcification, macrocalcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without macroalbuminuria. Methods: Participants without cardiovascular history were age and sex matched in three groups: nonT2DM controls, patients with T2DM without albuminuria (MA-), patients with T2DM with macroalbuminuria (MA+). [ 18 F]NaF activity was scored visually (in the aorta and femoral arteries) and was quantified as background activity (blood pool) corrected mean standardized uptake value of the abdominal aorta, and iliac arteries, expressed as target-to-background ratio (TBR). Arterial macrocalcification was assessed with computed tomography (CT) and arterial stiffness with carotid-femoral pulse wave velocity (PWV). Results: Three groups with comparable estimated Glomerular Filtration Rate were included (n=10 per group); controls 91 [81-104] vs MA- 87 [84-93] vs MA+ 85 [60-103] (median [IQR] mL/min*1.73m 2 ). Femoral [ 18 F]NaF uptake was significantly increased in the MA+ group (228 [100-446] vs 33 [0-93] in MA- (p=0.002) and vs 75 [0-200] in controls (p=0.052)), while other imaging markers were not. PWV was significantly higher in the MA+ group compared with MA- group (11.15 vs 8.86 m/s (p=0.009)) while no differences in pulse pressure were found. The [ 18 F]NaF activity in femoral arteries correlated with PWV (r=0.516, p=0.020) and pulse pressure (r=0.508, p=0.012). Conclusions: This study suggests that the presence of macroalbuminuria in patients with T2DM is an indication of early phased arterial disease prior to the development of irreversible macrocalcification. Although larger [ 18 F]NaF PET studies are needed, these results underline the importance of macroalbuminura in T2DM for detecting subclinical arterial disease at an early potentially reversible stage.

Local bone metabolism during the consolidation process of spinal interbody fusion.

Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. 18F sodium fluoride (18F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations. This study aimed to quantify the changes in local bone metabolism during consolidation of LIF. Six skeletally mature sheep underwent LIF surgery. 18F-NaF PET/CT scanning was performed 6 and 12weeks postoperatively to quantify the bone volume and metabolism in the operated segment. Bone metabolism was expressed as a function of bone volume. Early in the fusion process, bone metabolism was increased at the endplates of the operated vertebrae. In a next phase, bone metabolism increased in the center of the interbody region, peaked, and declined to an equilibrium state. During the entire postoperative time period of 12weeks, bone metabolism in the interbody region was higher than that of a reference site in the spinal column. Following LIF surgery, there is a rapid increase in bone metabolism at the vertebral endplates that develops towards the center of the interbody region. Knowing the local bone metabolism during uncompromised consolidation of spinal interbody fusion might enable identification of impaired bone formation early after LIF surgery using 18F-NaF PET/CT scanning.

Incidental Skeletal Findings on Sodium-fluoride Positron Emission Tomography: A Collection of Benign Tumors

Sodium-fluoride (NaF) positron emission tomography (PET) is a sensitive method to detect altered bone mineralization. Its increasing use in routine clinical practice for metastatic bone disease has also resulted in the detection or characterization of incidental benign bone lesions. A spectrum of NaF PET scan cases with benign bone tumors are presented in this article, including whole body PET bone scan and selected PET/computed tomography (CT), CT, or magnetic resonance imaging (MRI) of the region of interest. The reader will be able to improve their knowledge related to the clinical presentation of these entities, some are rare and recognize based on NaF PET and CT/MRI patterns by reviewing these cases.

SO07118F-SODIUM FLUORIDE POSITRON EMISSION TOMOGRAPHY AND BONE HISTOMORPHOMETRY - COMPARISON BETWEEN ONLY BONE TURNOVER -BASED AND EXPERT EVALUATION -BASED CLASSIFICATION OF RENAL OSTEODYSTROPHY

Abstract Background and Aims The diagnosis and the differentiation of renal osteodystrophy (ROD) are challenging. Bone biopsy is the golden standard, but it is invasive and not available in every center. Bone turnover rate is defined by bone formation rate and/or activation frequency. Adynamic bone disease is defined as low turnover bone with reduced osteoblast- and osteoclast activities. Hyperparahyreoid bone disease or osteitis fibrosa is defined as high turnover bone with osteoclast- and osteoblast activities and fibrosis. 18F- Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive imaging technique that allows assessment of regional bone turnover. The aim was to assess how well bone turnover –based classification of ROD correlates with the classification determined by an expert histomorphometrist (HK), and how these correlate with 18F-NaF PET analysis Method A total of 24 dialysis patients underwent a 18F-NaF PET scan. Fluoride activity was measured at the anterior iliac crest and in the lumbar region. An iliac crest bone biopsy was obtained within 4 weeks from the PET-scan. The diagnosis of bone histomorphometry was determined based on turnover-mineralization-volume (TMV) classification. Firstly, bone turnover was assessed using bone formation rate and activation frequency. Secondly, also other histomorphometric parameters (eg. osteoid volume, osteoid surface, resorption surface, mineralized surface, osteoblast and osteoclast surfaces and peritrabecular fibrosis) were also taking into account for classification of ROD by a histomorphometrist. Results Based on bone turnover parameters only, 12% of the patients had high turnover and 64% low turnover. When the diagnosis of renal osteodystrophy was made by a histomorphometrist, 40% had hyperparathyreoid bone/osteitis fibrosa and 24% adynamic bone disease or ostemalasia. 18F-NaF PET´s sensitivity to recognize hyperparathyreoid bone disease was 80% end specificity 100% (cut-of value 0.055).18F-NaF PET´s sensitivity to recognize adynamic bone disease was 100% and specificity 61% (cut-of value of fluoride-activity 0.038) Conclusion 18F-NaF PET works well as a diagnostic tool, when the diagnosis of ROD is based on the histopathological evaluation. It remains unknown how variations in normal bone turnover rate can be detected in CKD patients by 18F-NaF PET and if treatment decisions of ROD can be made only based on bone turnover.

Emerging Molecular Targets for Imaging of Atherosclerotic Plaque using Positron Emission Tomography.

Positron-emission-tomography (PET) using the radiopharmaceutical 18F-fluorodeoxyglucose (FDG) has become an established and validated molecular imaging modality for characterization of the inflammatory activity of atherosclerotic plaque. In the latest years, new innovative radiopharmaceuticals and applications have emerged, providing specific information on atherosclerotic plaque biology, particularly focused on inflammatory processes. To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers. A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the usefulness of nuclear hybrid imaging in atherosclerosis imaging using 18F-- sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET. Atherosclerosis imaging with PET using emerging, specific tracers holds promise in improving our understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. There is increasing, high-quality evidence on the usefulness of 18F-sodium fluoride PET and - to a lesser extent - CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy. F-sodium fluoride PET, CXCR4-targeted PET and amyloid-β-targeted PET may be used to obtain molecular information on different aspects of plaque biology. Further work is required to improve the technical aspects of these imaging techniques and to elucidate their ability to predict adverse cardiac events prospectively.

Locking and loading the bullet against micro-calcification.

Despite recent medical advances, cardiovascular disease remains the leading cause of death worldwide. As (micro)-calcification is a hallmark of atherosclerosis, this review will elaborately discuss advantages of sodium fluoride positron emission tomography (PET) as a reliable cardiovascular imaging technique for identifying the early onset of vascular calcification (i.e. locking onto the target). We assess state-of-the-art meta-analysis and clinical studies of possible treatment options and evaluate the concept of vitamin K supplementation to preserve vascular health (i.e. loading the bullet). After a structured PubMed search, we identified 18F-sodium fluoride (18F-NaF) PET as the most suitable technique for detecting micro-calcification. Presenting the pros and cons of available treatments, vitamin K supplementation should be considered as a possible safe and cost-effective option to inhibit vascular (micro)-calcification. This review demonstrates need for more extensive research in the concept of vitamin K supplementation (i.e. loading the bullet) and recommends monitoring the effects on vascular calcification using 18F-NaF PET (i.e. locking onto the target).

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging noninvasive approach for the treatment of oligometastases. Limited prospective evidence is available in breast cancer. ObjectivesTo determine the safety and feasibility of single fraction SABR for patients with bone only oligometastatic breast cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity and response assessment. Methods and materialsIn this single institution prospective trial we screened patients with computed tomography, bone scan, and sodium fluoride positron emission tomography. Eligible patients had one to three bone only oligometastases. All patients were treated at a dose of 20Gy in 1 fraction to each metastasis. Kaplan-Meier methods were used to determine local and distant progression free survival (LPFS and DPFS). Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. Results15 eligible patients were recruited to the study. Median follow-up time was 24 months. The treatment was feasible in 12 (80%) of patients with 3 (20%) of patients having treatment delayed by more than 3 days. 10 (67%) of patients experienced grade 1 treatment related toxicity, 4 (27%) experienced grade 2 toxicity and no patients experienced grade 3 or 4 treatment related toxicity. The two-year LPFS was 100%, DPFS was 67%. ConclusionWe observed that SABR is feasible, well tolerated and effective in this cohort with two thirds of patients disease-free at two years. In selected patients with bone-only oligometastatic disease, SABR could be considered a treatment option. Randomised trials are required to assess the impact of SABR on overall survival when compared to the standard of care.

NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy

IntroductionIn prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients.MethodsPatients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose.ResultsReduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to − 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy.Conclusion18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases.Trial registrationPOPSTAR, ‘Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy’, Universal Trial Number U1111-1140-7563, Registered 17th April 2013.

Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability using radiomic analysis of coronary computed tomography angiography.

AimsIdentification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability.Methods and resultsWe prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65–0.78 vs. 0.59, CI: 0.57–0.62; P < 0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72–0.88 vs. 0.66, CI: 0.58–0.73; P < 0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82–0.91 vs. 0.65, CI: 0.64–0.66; P < 0.001).ConclusionCoronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.

Development of sodium fluoride PET response criteria for solid tumours (NAFCIST) in a clinical trial of radium-223 in osteosarcoma: from RECIST to PERCIST to NAFCIST

PurposeThe development of osteosarcoma therapeutics has been challenging, in part because of the lack of appropriate criteria to evaluate responses. We developed a novel criteria in a clinical trial of radium-223 dichloride (223RaCl2) for response assessment in osteosarcoma, NAFCIST (Na18F PET response Criteria in Solid Tumors).Experimental designPatients received one to six cycles of 223RaCl2, and cumulative doses varied from 6.84 MBq to 57.81 MBq. Molecular imaging with technetium-99m phosphonate scintigraphy, fluorine-18-fluorodeoxyglucose (18FDG) positron emission tomography (PET) or sodium fluoride-18 (Na18F) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from Na18F PET.ResultsOf the 18 patients, 17 had bone lesions visible in at least one of the imaging studies. In four of seven patients with multiple skeletal lesions (>5), FDG PET and NaF PET studies could be compared. The skeletal tumour locations varied in our patient population: cranium=2, extremities=7, pelvis=10, spine=12 and thorax=9. The 18F-FDG PET and Na18F PET studies could be compared in all four patients who had multiple lung lesions (>5). Overall the Response Evaluation Criteria in Solid Tumors response was seen in one patient, but four patients experienced mixed responses better defined by Na18F PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of 223RaCl2 (r=− 0.53). NAFCIST correlated with overall survival (p value of 0.037) while the PERCIST (PET Response Criteria in Solid Tumors) did not (p value of 0.19).ConclusionsOur results indicate that Na18F PET should be further studied in osteosarcoma staging. NAFCIST may be a promising criteria for high-risk osteosarcoma response evaluation and correlates with survival. Further validation studies are needed.

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. ObjectiveTo determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. Design, setting, and participantsIn a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. InterventionA single fraction of 20-Gy SABR to each lesion. Results and limitationsBetween 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91–100) and 93% (95% CI: 84–100), and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. ConclusionsA single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. Patient summaryThis clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.

Initial experience with 18F-sodium fluoride (NaF) PET-CT: a viable functional biomarker in symptomatic Os acromiale.

Os acromiale (OA) is a failure of complete fusion of the acromial process. It is usually asymptomatic and discovered incidentally. OA can contribute to shoulder impingement symptoms and rotator cuff tears. 18F Sodium Fluoride (NaF) Positron Emission Tomography-CT (PET-CT) is an emerging and highly sensitive modality for oncological skeletal staging, and can show a variety of non-malignant uptake. We have analysed the relationship between 18F-NaF uptake in OA and associated symptoms of shoulder pain. Study population included 21 patients (mean age 60.2 ± 12years; 13 females and 8 males) with OA who underwent PET-CT scan by injecting 2.22MBqkg-1 of 18F-NaF. The relationship between 18F-NaF uptake and OA as a cause of pain was analysed. A 3-point grading system was used to evaluate uptake of 18F-NaF. In total 27 OA (12 symptomatic and 15 asymptomatic) were enrolled. All symptomatic OA showed focal increase tracer uptake of Grade 2, while asymptomatic OA did not have significant activity Grade 0 (n = 11) and Grade 1 (n = 4). 18F-NaF PET-CT appears to be a useful adjunct in the assessment of symptomatic OA with its particular strength being its high negative predictive value. Advances in knowledge: 18F-NaF PET-CT may be used as an ancillary tool for identifying symptomatic OA as a cause of shoulder pain in cases where other obvious causes of shoulder pain have been excluded.

18-Fluoride labeled sodium fluoride positron emission tomography with computer tomography: the impact of pretreatment staging in intermediate- and high-risk prostate cancer.

Background18-Fluoride labeled sodium fluoride (Na-18-F) positron emission tomography with computer tomography (PET/CT) has a better sensitivity and specificity than whole body bone scan (WBBS) in detecting osseous metastatic prostate cancer. We performed a pilot study of 20 men to examine what level of impact Na-18-F PET/CT has on management plans when used for staging newly diagnosed prostate cancer.Materials and methodsTwenty men were prospectively enrolled into the study in South Australia. Men were eligible if they had newly diagnosed, untreated, and biopsy-confirmed intermediate- or high-risk prostate cancer (D'Amico classification). WBBS and Na-18-F PET/CT scans were performed within 1 week of each other. Following review of the WBBS, treatment type and intent was documented by the treating urologist. The Na-18-F PET/CT scan was then reviewed. The impact of the Na-18-F PET/CT was measured on whether treatment modality or intent was subsequently altered: high impact = treatment intent or modality was changed; medium impact = treatment modality was modified; low impact = no change in treatment.ResultsIn 18 men (90%), the WBBS and Na-18-F PET/CT were negative for osseous metastases. In one man (5%), the WBBS demonstrated widespread osseous metastases which were similarly demonstrated on the Na-18-F PET/CT. One man (5%) had a normal WBBS; however, the Na-18-F PET/CT demonstrated widespread osseous metastases. Subsequently, in 19 men (95%), the results of the two scans were congruent and the addition of the Na-18-F PET/CT scan demonstrated a low impact on management. In one man (5%), the addition of the Na-18-F PET/CT had a high impact as treatment type and intent was altered.ConclusionsOur pilot study is the first of its kind in Australia, and our findings suggest that Na-18-F PET/CT is a safe and feasible modality for staging prostate cancer. However, its true impact on prostate cancer management warrants further investigation.