Increased lesion detectability in patients with locally advanced breast cancer-A pilot study using dynamic whole-body [18F]FDG PET/CT.

BACKGROUND: Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning in breast cancer. Evaluation of ALN is done by ultrasound, which is limited by inter-operator variability, and by sentinel lymph node biopsy and/or ALN dissection, none of which are without risks and/or long-term complications. It is known that conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limited sensitivity for ALN metastases. However, a recently developed dynamic whole-body (D-WB) [18F]FDG PET/CT scanning protocol, allowing for imaging of tissue [18F]FDG metabolic rate (MRFDG), has been shown to have the potential to increase lesion detectability. The study purpose was to examine detectability of malignant lesions in D-WB [18F]FDG PET/CT compared to conventional [18F]FDG PET/CT. RESULTS: This study prospectively included ten women with locally advanced breast cancer who were referred for an [18F]FDG PET/CT as part of their diagnostic work-up. They all underwent D-WB [18F]FDG PET/CT, consisting of a 6 min single bed dynamic scan over the chest region started at the time of tracer injection, a 64 min dynamic WB PET scan consisting of 16 continuous bed motion passes, and finally a contrast-enhanced CT scan, with generation of MRFDG parametric images. Lesion visibility was assessed by tumor-to-background and contrast-to-noise ratios using volumes of interest isocontouring tumors with a set limit of 50% of SUVmax and background volumes placed in the vicinity of tumors. Lesion visibility was best in the MRFDG images, with target-to-background values 2.28 (95% CI: 2.04-2.54) times higher than target-to-background values in SUV images, and contrast-to-noise values 1.23 (95% CI: 1.12-1.35) times higher than contrast-to-noise values in SUV images. Furthermore, five imaging experts visually assessed the images and three additional suspicious lesions were found in the MRFDG images compared to SUV images; one suspicious ALN, one suspicious parasternal lymph node, and one suspicious lesion located in the pelvic bone. CONCLUSIONS: D-WB [18F]FDG PET/CT with MRFDG images show potential for improved lesion detectability compared to conventional SUV images in locally advanced breast cancer. Further validation in larger cohorts is needed. CLINICAL TRIAL REGISTRATION: The trial is registered in clinicaltrials.gov, NCT05110443, https://www. CLINICALTRIALS: gov/study/NCT05110443?term=NCT05110443&rank=1 .

Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends.

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides.

Dynamic whole-body [18F]FES PET/CT increases lesion visibility in patients with metastatic breast cancer.

BACKGROUND: Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images ( K i ) are quantitative and improve lesion visibility. RESULTS: This prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. K i values from Patlak parametric images correlated with K i values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric K i images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25-2.68) and CNR 1.17 (95% CI: 1.08-1.26) times higher in K i images compared to SUV images. These quantitative differences were seen as reduced background activity in the K i images. CONCLUSION: [18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric K i images, with superior lesion visibility and K i values comparable to K i values found from full kinetic analyses. This may aid correct ER classification and treatment decisions. Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731.

Effects of exogenous lactate on lipid, protein, and glucose metabolism-a randomized crossover trial in healthy males.

Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. In a single-blind, randomized, crossover design, eight healthy men were studied after an overnight fast on two occasions: 1) during a sodium-lactate infusion (LAC) and 2) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRdglu) were evaluated using [9,10-3H]palmitate and [3-3H]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [15N]phenylalanine, [2H4]tyrosine, [15N]tyrosine, and [13C]urea tracers. In the postabsorptive period, plasma lactate increased to 2.7 ± 0.5 mmol/L during LAC vs. 0.6 ± 0.3 mmol/L during CTR (P < 0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared with CTR (84 ± 32 µmol/min vs. 120 ± 35 µmol/min, P = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (P = 0.7). EGP, ΔRdglu, and M value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux (P = 0.02) and protein synthesis (P = 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole body phenylalanine flux was increased. Clinical trial registrations: NCT04710875.NEW & NOTEWORTHY Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.

Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes.

AIMS: Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance. METHODS: Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model. RESULTS: Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, µmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, µmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, µmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14 ± 9, 10-9 min-1, p < 0.01) and glucose effectiveness (2.6 × 10-2 ± 0.3 × 10-2 vs. 2.4 × 10-2 ± 0.3 × 10-2, dL/kg/min, p = 0.02). CONCLUSIONS: Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET.

BACKGROUND: Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). METHODS: Thirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. RESULTS: The results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min). CONCLUSIONS: Agreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.

OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).

The impact of CHOP versus bendamustine on bone mineral density in patients with indolent lymphoma enrolled in the GALLIUM study.

Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients. Patients in this GALLIUM post hoc study were ≥60 years old and in complete remission at induction treatment completion (ITC), following treatment with G or R in combination with bendamustine or CHOP. To assess BMD, Hounsfield units (HU) were measured in lumbar vertebra L1 on annual computed tomography. Furthermore, vertebral compression fractures were recorded. Of 173 patients included, 59 (34%) received CHOP and 114 (66%) received bendamustine. At baseline, there was no difference in HU between groups. The mean HU decrease from baseline to ITC was 27.8 after CHOP and 17.3 after bendamustine, corresponding to a difference of 10.4 (95% CI: 3.2-17.6). Vertebral fractures were recorded in 5/59 patients receiving CHOP and in 2/114 receiving bendamustine. CHOP was associated with a significant greater decrease in BMD and more frequent fractures. These results suggest that prophylaxis against BMD loss should be considered.

Single time point quantitation of cerebral glucose metabolism by FDG-PET without arterial sampling.

BACKGROUND: Until recently, quantitation of the net influx of 2-[18F]fluorodeoxyglucose (FDG) to brain (Ki) and the cerebrometabolic rate for glucose (CMRglc) required serial arterial blood sampling in conjunction with dynamic positron emission tomography (PET) recordings. Recent technical innovations enable the identification of an image-derived input function (IDIF) from vascular structures, but are frequently still encumbered by the need for interrupted sequences or prolonged recordings that are seldom available outside of a research setting. In this study, we tested simplified methods for quantitation of FDG-Ki by linear graphic analysis relative to the descending aorta IDIF in oncology patients examined using a Biograph Vision 600 PET/CT with continuous bed motion (Aarhus) or using a recently installed Biograph Vision Quadra long-axial field-of-view (FOV) scanner (Bern). RESULTS: Correlation analysis of the coefficients of a tri-exponential decomposition of the IDIFs measured during 67 min revealed strong relationships among the total area under the curve (AUC), the terminal normalized arterial integral (theta(52-67 min)), and the terminal image-derived arterial FDG concentration (Ca(52-67 min)). These relationships enabled estimation of the missing AUC from late recordings of the IDIF, from which we then calculated FDG-Ki in brain by two-point linear graphic analysis using a population mean ordinate intercept and the single late frame. Furthermore, certain aspects of the IDIF data from Aarhus showed a marked age-dependence, which was not hitherto reported for the case of FDG pharmacokinetics. CONCLUSIONS: The observed interrelationships between pharmacokinetic parameters in the IDIF measured during the PET recording support quantitation of FDG-Ki in brain using a single averaged frame from the interval 52-67 min post-injection, with minimal error relative to calculation from the complete dynamic sequences.

Detection and correction of patient motion in dynamic 15O-water PET MPI.

BACKGROUND: Patient motion constitutes a limitation to 15O-water cardiac PET imaging. We examined the ability of image readers to detect and correct patient motion using simulated motion data and clinical patient scans. METHODS: Simulated data consisting of 16 motions applied to 10 motion-free scans were motion corrected using two approaches, pre-analysis and post-analysis for motion identification. Both approaches employed a manual frame-by-frame correction method. In addition, a clinical cohort was analyzed for assessment of prevalence and effect of motion and motion correction. RESULTS: Motion correction was performed on 94% (pre-analysis) and 64% (post-analysis) of the scans. Large motion artifacts were corrected in 91% (pre-analysis) and 74% (post-analysis) of scans. Artifacts in MBF were reduced in 56% (pre-analysis) and 58% (post-analysis) of the scans. The prevalence of motion in the clinical patient cohort (n = 762) was 10%. Motion correction altered exam interpretation in only 10 (1.3%) clinical patient exams. CONCLUSION: Frame-by-frame motion correction after visual inspection is useful in reducing motion artifacts in cardiac 15O-water PET. Reviewing the initial results (parametric images and polar maps) as part of the motion correction process, reduced erroneous corrections in motion-free scans. In a large clinical cohort, the impact of motion correction was limited to few patients.

Exercise increases myocardial free fatty acid oxidation in subjects with metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with dyslipidemia and may promote cardiac lipotoxicity. Myocardial free fatty acids (FFA) oxidation (MOFFA) is normal in pre-diabetes, but reduced in heart failure. We hypothesized that during exercise MOFFA, very low-density lipoprotein triglycerides (VLDL-TG) secretion, hepatic FFA utilization, and lactate production differ among obese subjects with and without MAFLD. METHODS: Nine obese subjects with MAFLD and 8 matched subjects without MAFLD (Control) without a history of heart failure and cardiovascular disease were compared before and after 90-min exercise at 50% Peak oxygen consumption. Basal and exercise induced cardiac and hepatic FFA oxidation, uptake and re-esterification and VLDL-TG secretion were measured using [11C]palmitate positron-emission tomography and [1-14C]VLDL-TG. RESULTS: In the heart, increased MOFFA was observed after exercise in MAFLD, whereas MOFFA decreased in Control (basal vs exercise, MAFLD: 4.1 (0.8) vs 4.8 (0.8) µmol·100 ml-1 min-1; Control: 4.9 (1.8) vs 4.0 (1.1); µmol·100 ml-1 min-1, mean (SD), p < 0.048). Hepatic FFA fluxes were significantly lower in MAFLD than Control and increased ≈ two-fold in both groups. VLDL-TG secretion was 50% greater in MAFLD at rest and similarly suppressed during exercise. Plasma lactate increased significantly less in MAFLD than Control during exercise. CONCLUSIONS: Using robust tracer-techniques we found that obese subjects with MAFLD do not downregulate MOFFA during exercise compared to Control, possibly due to diminished lactate supply. Hepatic FFA fluxes are significantly lower in MAFLD than Control, but increase similarly with exercise. VLDL-TG export remains greater in MAFLD compared to Control. Basal and post-exercise myocardial and hepatic FFA, VLDL-TG and lactate metabolism is abnormal in subjects with MAFLD compared to Control.

Multiparametric dynamic whole-body PSMA PET/CT using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007.

BACKGROUND: Routine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability. METHODS: Twenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [68Ga]Ga-PSMA-11 and ten with [18F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (Ki and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared. RESULTS: The two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [68Ga]Ga-PSMA-11 and irreversible for [18F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images. CONCLUSION: D-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [18F]PSMA-1007 should be preferred over [68Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions.

Coronary Artery Stenosis Evaluation by Angiography-Derived FFR: Validation by Positron Emission Tomography and Invasive Thermodilution.

BACKGROUND: Fractional flow reserve (FFR) derived from invasive coronary angiography (QFR) is promising for evaluation of intermediate coronary artery stenosis. OBJECTIVES: The authors aimed to compare the diagnostic performance of QFR and the guideline-recommended invasive FFR using 82Rubidium positron emission tomography (82Rb-PET) myocardial perfusion imaging as reference standard. METHODS: This is a prospective, observational study of symptomatic patients with suspected obstructive coronary artery disease on coronary computed tomography angiography (≥50% diameter stenosis in ≥1 vessel). All patients were referred to 82Rb-PET and invasive coronary angiography with FFR and QFR assessment of all intermediate (30%-90% diameter stenosis) stenoses. Main analyses included a comparison of the ability of QFR and FFR to identify reduced myocardial blood flow (<2 mL/g/min) during vasodilation and/or relative perfusion abnormalities (summed stress score ≥4 in ≥2 adjacent segments). RESULTS: A total of 250 patients (320 vessels) with indication for invasive physiological assessment were included. The continuous relationship of 82Rb-PET stress myocardial blood flow per 0.10 increase in FFR was +0.14 mL/g/min (95% CI: 0.07-0.21 mL/g/min) and +0.08 mL/g/min (95% CI: 0.02-0.14 mL/g/min) per 0.10 QFR increase. Using 82Rb-PET as reference, QFR and FFR had similar diagnostic performance on both a per-patient level (accuracy: 73%; 95% CI: 67%-79%; vs accuracy: 71%; 95% CI: 64%-78%) and per-vessel level (accuracy: 70%; 95% CI: 64%-75%; vs accuracy: 68%; 95% CI: 62%-73%). The per-vessel feasibility was 84% (95% CI: 80%-88%) for QFR and 88% (95% CI: 85%-92%) for FFR by intention-to-diagnose analysis. CONCLUSIONS: With 82Rb-PET as reference modality, the wire-free QFR solution showed similar diagnostic accuracy as invasive FFR in evaluation of intermediate coronary stenosis. (DAN-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease; NCT02264717).

Inclusion of Metabolic Tumor Volume in Prognostic Models of Bone and Soft Tissue Sarcoma Increases the Prognostic Value.

Sarcomas are rare and have a high mortality rate. Further prognostic classification, with readily available parameters, is warranted, and several studies have examined circulating biomarkers and PET parameters separately. This single-site, retrospective study aimed to examine the prognostic values of several scoring systems in combination with PET parameters. We included 148 patients with sarcoma, who were treated and scanned at Aarhus University Hospital from 1 January 2016 to 31 December 2019. The Akaike information criterion and Harrell's concordance index were used to evaluate whether the PET parameters added prognostic information to existing prognostic models using circulating biomarkers. Of the PET parameters, metabolic tumor volume (MTV) performed best, and when combined with the existing prognostic models, the prognostic value improved in all models. Backward stepwise selection was used to create a new model, SBSpib, which included albumin, lymphocytes, and one PET parameter, MTV. It has scores ranging from zero to three and increasing hazard ratios; HR = 4.83 (1.02-22.75) for group one, HR = 7.40 (1.6-33.42) for group two, and HR = 17.32 (3.45-86.93) for group three. Consequently, implementing PET parameters in prognostic models improved the prognostic value. SBSpib is a new prognostic model that includes both circulating biomarkers and PET parameters; however, validation in another sarcoma cohort is warranted.

Ultrasonography in the assessment of disease activity in cranial and large-vessel giant cell arteritis: a prospective follow-up study.

OBJECTIVES: We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients. METHODS: Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values. RESULTS: Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate-strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8. CONCLUSIONS: The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response.

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

Clinical validation of a population-based input function for 20-min dynamic whole-body 18F-FDG multiparametric PET imaging.

PURPOSE: Contemporary PET/CT scanners can use 70-min dynamic whole-body (D-WB) PET to generate more quantitative information about FDG uptake than just the SUV by generating parametric images of FDG metabolic rate (MRFDG). The analysis requires the late (50-70 min) D-WB tissue data combined with the full (0-70 min) arterial input function (AIF). Our aim was to assess whether the use of a scaled population-based input function (sPBIF) obviates the need for the early D-WB PET acquisition and allows for a clinically feasible 20-min D-WB PET examination. METHODS: A PBIF was calculated based on AIFs from 20 patients that were D-WB PET scanned for 120 min with simultaneous arterial blood sampling. MRFDG imaging using PBIF requires that the area under the curve (AUC) of the sPBIF is equal to the AUC of the individual patient's input function because sPBIF AUC bias translates into MRFDG bias. Special patient characteristics could affect the shape of their AIF. Thus, we validated the use of PBIF in 171 patients that were divided into 12 subgroups according to the following characteristics: diabetes, cardiac ejection fraction, blood pressure, weight, eGFR and age. For each patient, the PBIF was scaled to the aorta image-derived input function (IDIF) to calculate a sPBIF, and the AUC bias was calculated. RESULTS: We found excellent agreement between the AIF and IDIF at all times. For the clinical validation, the use of sPBIF led to an acceptable AUC bias of 1-5% in most subgroups except for patients with diabetes or patients with low eGFR, where the biases were marginally higher at 7%. Multiparametric MRFDG images based on a short 20-min D-WB PET and sPBIF were visually indistinguishable from images produced by the full 70-min D-WB PET and individual IDIF. CONCLUSIONS: A short 20-min D-WB PET examination using PBIF can be used for multiparametric imaging without compromising the image quality or precision of MRFDG. The D-WB PET examination may therefore be used in clinical routine for a wide range of patients, potentially allowing for more precise quantification in e.g. treatment response imaging.

SGLT2 inhibition reduces myocardial oxygen consumption.

Aims/hypothesis: SGLT2 inhibition is associated with a reduced risk of cardiac disease that is still largely unexplained. According to one hypothesis, improved myocardial energetics may explain the cardioprotective effects of SGLT2i. However, recent mechanistic studies that have addressed this question have lacked the power to detect discrete but still clinically significant effects. Methods: We pooled data from two recent randomized clinical trials and performed a meta-analysis to determine the effect of SGLT2 inhibition on myocardial oxygen consumption and myocardial external efficiency measured by positron emission tomography. Results: SGLT2 inhibition reduced myocardial oxygen consumption (-1.06 [95%CI: 0.22-1.89] mL/100 g/min (n = 59, p = 0.01)), but did not affect myocardial external efficiency (2.22 [95%CI: 0.66-5.11] % (n = 59, p = 0.13)). Conclusions: /interpretation: SGLT2 inhibition reduces myocardial oxygen consumption at rest, which may contribute to the drugs' cardioprotective effects.

Clinical feasibility and impact of data-driven respiratory motion compensation studied in 200 whole-body 18F-FDG PET/CT scans.

BACKGROUND: This study examines the clinical feasibility and impact of implementing a fully automated whole-body PET protocol with data-driven respiratory gating in patients with a broad range of oncological and non-oncological pathologies 592 FDG PET/CT patients were prospectively included. 200 patients with lesions in the torso were selected for further analysis, and ungated (UG), belt gated (BG) and data-driven gating (DDG) images were reconstructed. All images were reconstructed using the same data and without prolonged acquisition time for gated images. Images were quantitatively analysed for lesion uptake and metabolic volume, complemented by a qualitative analysis of visual lesion detection. In addition, the impact of gating on treatment response evaluation was evaluated in 23 patients with malignant lymphoma. RESULTS: Placement of the belt needed for BG was associated with problems in 27% of the BG scans, whereas no issues were reported using DDG imaging. For lesion quantification, DDG and BG images had significantly greater SUV values and smaller volumes than UG. The physicians reported notable image blurring in 44% of the UG images that was problematic for clinical evaluation in 4.5% of cases. CONCLUSION: Respiratory motion compensation using DDG is readily integrated into clinical routine and produce images with more accurate and significantly greater SUV values and smaller metabolic volumes. In our broad cohort of patients, the physicians overwhelmingly preferred gated over ungated images, with a slight preference for DDG images. However, even in patients with malignant disease in the torso, no additional diagnostic information was obtained by the gated images that could not be derived from the ungated images.