Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

Comparison of the diagnostic value of 18F-NaF PET/CT and 99mTc-MDP SPECT for bone metastases: a systematic review and meta-analysis.

Background: Bone scintigraphy, the standard tool for detecting bone metastases has some insufficiencies; thus, supplementary imaging techniques are needed. This study is a comprehensive meta-analysis of studies reporting and comparing the diagnostic efficacy of 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) and 99mTc-MDP single-photon emission computed tomography (SPECT) for bone metastases. Methods: Literature related to the diagnosis of bone metastases using 18F-NaF PET/CT and 99mTc-MDP SPECT was searched on PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang databases, and VIP. Evaluation of study quality was performed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Pooled sensitivity (SEN) and specificity (SPE) were assessed along with heterogeneity. The subject operating characteristic curve was plotted, the area under the curve (AUC) was calculated, and the pre- and post-test probabilities were compared. Results: Finally, 11 articles, consisting of 1,085 patients and 1,782 lesions, were included. At the patient level (11 articles), the results were pooled SEN =0.92 and SPE =0.96 for PET/CT, SEN =0.80 and SPE =0.90 for SPECT. The AUC of PET/CT [0.98 (0.96-0.99)] was higher than that of SPECT [0.92 (0.89-0.94), P<0.05]. At the lesion level (6 articles), the results were pooled SEN =0.96 and SPE =0.98 for PET/CT, SEN =0.76 and SPE =0.94 for SPECT. The AUC of PET/CT [0.99 (0.98-1.00)] was higher than that of SPECT [0.94 (0.92-0.96); P<0.05]. Statistical heterogeneity existed, and meta-regression showed that, at patient-based level, the study design type, tumor character, and the selection blinding method were the main sources of heterogeneity. Furthermore, both PET/CT and SPECT had superior SEN for osteogenic metastases than non-osteogenic metastases (P=0.01). At the lesion level, tumor character was a source of heterogeneity accompanied by an increased SEN for osteogenic metastases, and the SEN for SPECT combined with CT was improved [SEN =0.87 (0.68-1.00), P=0.03]. Conclusions: 18F-NaF PET/CT has a higher SEN and SPE than 99mTc-MDP SPECT in diagnosing bone metastases, nevertheless, it is necessary to fully understand the primary tumor and the characteristics of the imaging protocol to choose suitable modality for individuals. Combining SPECT with CT improves the diagnostic efficacy than having SPECT alone and can be a powerful supplement to PET/CT for suspected osteogenic bone metastases.

The influence of CT and dual-energy X-ray absorptiometry (DXA) bone density on quantitative [18F] sodium fluoride PET.

BACKGROUND: [18F] sodium fluoride PET/CT provides quantitative measures of bone metabolic activity expressed by the parameters standardised uptake value (SUV) and bone plasma clearance (K i) that correlate with measurements of bone formation rate obtained by bone biopsy with double tetracycline labelling. Both SUV and K i relate to the tracer uptake in each millilitre of tissue. In general, the bone region of interest (ROI) includes both mineralised bone {generally with a high concentration of [18F]NaF} and bone marrow (with a much lower concentration), suggesting that correcting SUV and K i for volumetric bone mineral density (vBMD) and measuring them with respect to the tracer uptake in each gram of bone mineral might improve the correlation with the findings of bone biopsy. As a first test of this hypothesis, we looked for positive correlations between SUV and K i values with CT and DXA bone mineral density (BMD) parameters measured in the same ROI. METHODS: A retrospective reanalysis was performed of 63 lumbar spine [18F]NaF PET/CT scans acquired in four earlier studies. The quantitative PET parameters SUV and K i were measured in L1-L4 and Hounsfield units (HU) measured on the CT scans in the same ROI. Spine BMD data was also obtained from DXA scans in the form of areal BMD and used to derive the bone mineral apparent density (BMAD, an estimate of vBMD). Scatter plots were drawn of SUV and K i against HU, BMAD and areal BMD and the Spearman rank correlation coefficients derived for each plot. RESULTS: All correlations were positive and statistically significant. Correlations were highest for HU (SUV: RS =0.513, P<0.0001; K i: RS =0.429, P=0.0005) and lowest for areal BMD (SUV: RS =0.353, P=0.005; K i: RS =0.274, P=0.03). CONCLUSIONS: The results demonstrate significant positive correlations between SUV and K i and vBMD measurements in the form of HU from CT or BMAD and areal BMD from DXA. These findings justify further exploration of the relationship between SUV and K i [18F]NaF PET/CT measurements and CT or DXA measurements of vBMD to examine whether normalization for bone density might improve their correlation with bone metabolic activity as measured by bone biopsy.

18F-sodium fluoride positron emission tomography assessed microcalcifications in culprit and non-culprit human carotid plaques.

BACKGROUND: 18F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18F-NaF uptake with calcification visualized on microcomputed tomography (microCT). METHODS: Carotid plaques from stroke patients undergoing surgery were incubated in 18F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. RESULTS: 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18F-NaF PET VOI showed calcification on CT. CONCLUSIONS: 18F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by 18F-sodium fluoride PET/CT.

PURPOSE: Our aim was to assess whether 18F-NaF PET/CT is able to predict progression of the CT calcium score. METHODS: Between August 2007 and November 2015, 34 patients (18 women, 16 men; age, mean ± standard deviation, 57.5 ± 13.9 years; age range 19-78 years) with malignancy or orthopaedic disease were enrolled in this study, with approximately 1-year follow-up data. Baseline and follow-up CT images were retrospectively evaluated for the presence of calcification sites in major vessel walls. The maximum and mean CT values (CTmax and CTmean, in Hounsfield units), calcification volumetric score (CVS, in cubic millimetres) and Agatston units score (AU) were evaluated for each site. Subsequent changes in CTmax, CTmean, CVS and AU were calculated and expressed as ΔCTmax, ΔCTmean, ΔCVS and ΔAU, respectively. We then evaluated the relationship between 18F-NaF uptake (using the maximum target-to-background ratio, TBRmax, and the maximum blood-subtracted 18F-NaF activity, bsNaFmax, which was obtained by subtracting the SUVmax of each calcified plaque lesion and NaF-avid site from the SUVmean in the right atrium blood pool) and the change in calcified plaque volume and characteristics obtained after 1 year. RESULTS: We detected and analysed 182 calcified plaque sites and 96 hot spots on major vessel walls. 18F-NaF uptake showed very weak correlations with CTmax, CTmean, CVS, CVS after 1 year, AU and AU after 1 year on both baseline and follow-up PET/CT scans for each site. 18F-NaF uptake showed no correlation with ΔCTmax or ΔCTmean. However, there was a significant correlation between the intensity of 18F-NaF uptake and ΔCVS and ΔAU. CONCLUSION: 18F-NaF uptake has a strong correlation with calcium score progression which was a predictor of future cardiovascular disease risk. PET/CT using 18F-NaF may be able to predict calcium score progression which is known to be the major characteristic of atherosclerosis.

[18F]-Sodium fluoride uptake in Takayasu arteritis.

BACKGROUND: While 18F-fluorodeoxyglucose and 18F-sodium fluoride with positron emission tomography relate with inflammation and calcification, their role in the assessment of patients with Takayasu arteritis has not yet been studied. METHODS: We present 5 patients with suspected active metabolic disease who underwent PET with 18F-fluorodeoxyglucose and 18F-sodium fluoride in order to explore the locations and correlations of 18F-fluorodeoxyglucose and 18F-sodium fluoride uptakes. Diagnosis of metabolic active disease was based on 18F-fluorodeoxyglucose uptake. RESULTS: We studied 3 female patients and 2 male patients. Median age was 29 years (min: 19 max: 63). In areas with atherosclerotic plaques, we found a negative correlation between 18F-sodium fluoride and 18F-fluorodeoxyglucose uptakes (r = -0.78) (P = .001). Meanwhile, in areas with only metabolic active disease, we found a positive correlation between 18F-sodium fluoride and 18F-fluorodeoxyglucose uptakes (r = 0.94) (P = .019). CONCLUSIONS: In Takayasu arteritis, 18F-sodium fluoride uptake can document different stages of metabolic disease, even in the absence of active metabolic disease or symptoms.