Blood Pool Activity Research Articles

SPECT/CT Quantification of 99m-TC PYP Uptake to Assess Tafamidis Treatment Response in ATTR Cardiac Amyloidosis

BackgroundCardiac imaging with bone-avid tracers for the diagnosis of ATTR cardiac amyloidosis employs only limited quantification, but SPECT/CT acquisition can provide volumetric assessment with quantification of tracer uptake. Tafamidis is routinely used in the treatment of cardiac amyloidosis but there is scant data on changes in imaging results during therapy. The purpose of this study was to perform longitudinal assessment of Tc-99m-PYP imaging to determine if tafamidis therapy results in any change in quantitative measures of tracer uptake. MethodsA prospective, single-center study of ATTR patients being treated with tafamidis using Tc-99m-PYP SPECT/CT to quantify cardiac tracer uptake in the whole heart and left ventricle. Standardized uptake values (SUVs) were adjusted for blood pool activity. Comparison of baseline activity was made to values obtained approximately every 6 months during treatment. ResultsTwenty-two patients (77.0 ± 7.5 years old, 86.4% male) were on tafamidis for 15.3 ± 4.0 months with an average time between baseline and final follow-up study of 16.8 ± 4.7 months. Thirteen (59.1%) had multiple follow-up amyloid studies. Statistically significant reductions in total SUVs, SUV volume, and percentage of injected dose were seen. Adjusted for the maximal aortic SUV, the total SUV’s in the left ventricle decreased by 36.9%, the SUV volume by 38.7%, and the percentage of injected dose decreased by 34.9% (all p-values ≤0.0001). Over the study duration there was a decrease of 7.7%/month in the measured metrics. ConclusionThe quantitative SUV measurements from Tc-99m-PYP SPECT/CT revealed an overall decrease in scintographic amyloid burden during the course of tafamidis therapy, but additional work is needed to determine the optimal metrics and improve the reproducibility of the quantification.

Head-to-head comparison of 18F-sodium fluoride coronary PET imaging between a silicon photomultiplier with digital photon counting and conventional scanners

BackgroundWe compared silicone photomultipliers with digital photon counting (SiPM) and photomultiplier tubes (PMT) PET in imaging coronary plaque activity with 18F-sodium fluoride (18F-NaF) and evaluated comprehensively SiPM PET reconstruction settings. MethodsIn 25 cardiovascular disease patients (mean age 67±12 years), we conducted 18F-NaF PET on a SiPM (Biograph Vision) and conventional PET (Discovery 710) on the same day as part of a prospective clinical trial (NCT03689946). Following administration of 250 MBq of 18F-NaF, patients underwent a contrast-enhanced CT angiography and a 30-min PET acquisition in list mode on each PET consecutively. Image noise was defined as mean standard deviation of blood pool activity within the left atria. Target-to-background ratio (TBR) and signal-to-noise ratio (SNR) were measured within the whole-vessel tubular 3-dimensional volumes of interest on the cardiac motion and attenuation corrected 18F-NaF PET images using dedicated software. ResultsThere were significant differences in image noise and background activity between the two PETs (Image noise (%), PMT: 7.6±3.7 vs. SiPM: 4.0±2.3, p<0.001; background activity, PMT: 1.4±0.4 vs. SiPM: 1.0±0.3, p<0.001). Similarly, the SNR and TBR were significantly higher in vessels scanned with the SiPM PET (SNR, PMT: 16.3±11.5 vs. SiPM: 32.7±29.8, p<0.001; TBR, PMT: 0.8±0.4 vs. SiPM: 1.1±0.6, p<0.001). SiPM PET image reconstruction with a 256 matrix, 1.4 mm pixel, and 2 mm Gaussian filter provided best tradeoff in terms of maximal SNR, TBR and clinically practical file size. ConclusionsIn 18F-NaF coronary PET imaging, the SiPM PET showed superior image contrast and less image noise compared to PMT PET.

Reduced Prevalence of Significant Blood Pool Activity With Tc-99m HDP Imaging for ATTR Cardiac Amyloidosis

Reduced Prevalence of Significant Blood Pool Activity With Tc-99m HDP Imaging for ATTR Cardiac Amyloidosis

Quantitative 99mTc-pyrophosphate myocardial uptake: Changes on transthyretin stabilization therapy

BackgroundQuantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography (99mTc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99mTc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function. MethodsThis prospective longitudinal cohort study investigated changes in 99mTc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVs) (SUVmax, SUVmean), cardiac amyloid activity (CAA; SUVmean∗LV activity volume), and percent injected dose (%ID) (mean activity concentration∗LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test. ResultsFollowing therapy, visual grade decreased significantly (P = 0.003). Several quantitative 99mTc-PYP metrics also decreased significantly: SUVmax (median −0.75, P = 0.011), CAA (median: −406.6, P < 0.001), and %ID (median: −0.45, P < 0.001). Serum transthyretin levels improved (median: +6.5 mg/dL, P = 0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, and LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable. ConclusionsFavorable changes in 99mTc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, whereas echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than amyloid burden regression. Further investigation is needed to understand the implications of these findings.

Abstract 2583: [68Ga]Ga-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging

Abstract Introduction &amp; Purpose: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. To date, the imaging of HCC is difficult, insufficient for disease staging and barely improved over the past decades. Glypican-3 (GPC3) is a cell-surface receptor highly expressed by HCC and of diagnostic and prognostic value. GPC3 has been reported as potential target for diagnosis and treatment of HCC for nuclear theranostics. RYZ-GPC3 is a DOTA modified macrocyclic peptide with high affinity for GPC3, which may allow PET imaging or nuclear therapy. Here we report the first clinical results of [68Ga]Ga-RYZ-GPC3 PET-imaging in patients with known or suspected HCC. Methods: [68Ga]Ga-RYZ-GPC3 was obtained upon labeling the peptide precursor with 68Ga from a 68Ge/68Ga-generator and heating till 90⁰C for 10 min followed by sterile filtration. After administration of 2 MBq/kg [68Ga]Ga-RYZ-GPC3, a 60 min dynamic PET scan was acquired or multiple static PET/CT were acquired at 20 min, 1, 2 and 4 hours. Besides qualitative interpretation, standardized uptake values (SUVmax, SUVmean) were measured in various compartments; HCC lesions, healthy liver (HL), kidneys, blood pool activity in the left ventricle (BP) and gastric fundus. Additionally, tumor-to-healthy liver ratios (TLR) were calculated: SUVmean,HCC divided by SUVmean,HL. Results: Radiolabeling to obtain [68Ga]Ga-RYZ-GPC3 was near quantitative, making the production highly reliable. Eleven patients (4 patients dynamic; 7 patients static protocol) were scanned. One patient did not have an HCC. Another patient had a concurrent metastatic prostate adenocarcinoma, which did not show uptake, both qualitatively and quantitatively. All HCC lesions showed uptake in qualitative assessment, even in immunohistochemistry confirmed GPC3-negative HCC lesions (3 lesions). In 23 HCC lesions, including the aforementioned GPC3-negative lesions, mean SUVmax was 17.9 (range 2.7-95.3) and mean SUVmean was 10.2 (range 1.0-49.2) at 60 minutes. Uptake in HL and BP decrease over time and become negligible 45 minutes after administration (SUVmean &amp;lt;1.5). The opposite occurs for HCC and TLR, which continuously increase up to 4 hours after administration (TLR 4.4 to 19.2, at 18 minutes and 4 hours respectively). In individual lesion analysis, TLR was the highest at 60 or 120 minutes post-injection scans. Uptake in the gastric fundus, gradually increases in the first hour, and decreases gradually afterwards (SUVmean from 4.0 to 12.7, back to 10.1). Conclusions: [68Ga]Ga-RYZ-GPC3 is the first peptide based PET tracer that allows the high quality molecular imaging of HCC. Thereby [68Ga]Ga-RYZ-GPC3 is suitable for the selective diagnosis of HCC. In addition, based on the biodistribution and in vivo dynamics on these diagnostic images, RYZ-GPC3 is very likely to hold therapeutic potential upon labeling with a therapeutic isotope (e.g 177Lu or 225Ac). Citation Format: Arthur J.A.T. Braat, Alex J. Poot, Constantin Lapa, Marnix G.E.H. Lam, Wolfgang A. Weber, Anna Karmann, Ye Yuan, Jessica Rearden, Ken Song, Ralph A. Bundschuh. [68Ga]Ga-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2583.

18F-FDG PET/CT Correctly Differentiates Idiopathic Pericarditis from Recurrent Lymphoma in a Patient with Primary Mediastinal Lymphoma.

A man in his 30s awaiting end-of-treatment 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) for primary mediastinal B-cell lymphoma developed chest pain and pericardial effusion. His interim 18F-FDG PET/CT showed complete metabolic responses. His blood test revealed elevated levels of inflammatory markers, including C-reactive protein of 204.1 mg/L and erythrocyte sedimentation rate of 106 mm/h. His pericardial biopsy revealed organizing fibrinous pericarditis with hemosiderin pigment deposition and no evidence of malignancy or granuloma. The 18F-FDG PET/CT performed during this episode of illness revealed a mild degree of 18F-FDG uptake along the pericardial lining [maximum standardized uptake value (SUVmax) =6.76] compared with the blood pool activity (SUVmax =3.17), which favors pericarditis over relapsed lymphoma. His symptoms subsided 2 weeks after treatment with an non-steroidal anti-inflammatory drug, and he had no sign of relapsed lymphoma on subsequent follow-ups.

Thoracic aortic microcalcification activity in combined positron emission tomography and magnetic resonance imaging

IntroductionNon-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [18F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [18F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve,MethodsThirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [18F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [18F]fluoride uptake on PET-CT and PET-MRI.ResultsAortic sodium [18F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2.ConclusionAscending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required.

Altered biodistribution of [68Ga]Ga-DOTA-TOC during somatostatin analogue treatment.

The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5days, there was a significantly higher bloodpool activity than at longer intervals. Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5days after the injection of lanreotide.

Physiological 68Ga-PSMA-11 Uptake in Dural Venous Sinuses.

We describe hitherto unreported physiological low-grade 68Ga-PSMA-11 uptake in dural sinuses of patients who underwent 68Ga-PSMA-11 PET/CT for evaluation of prostate carcinoma. A strong positive correlation was found between SUVmax of tracer uptake in dural sinuses and SUVmax of blood pool activity in superior vena cava. Low-grade 68Ga-PSMA-11 uptake seen in dural sinuses is physiological and is most likely result of venous blood pool activity. Such uptake should not be interpreted as pathological. Knowledge of such physiological uptake is essential for optimal interpretation of PSMA PET/CT images and differentiating physiological versus pathological uptake.

Abstract B043: Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer

Abstract Breast cancer is the most common cause of mortality among women worldwide. Among all subtypes, HER2-positive breast cancers are highly aggressive and have poor prognosis. Surgical resection is choice of treatment. However, surgery may not be possible if disease is widespread. Trastuzumab, a monoclonal antibody, is globally used for immunotherapy. It is a large sized molecule (141kDa) and show slow pharmacokinetics and high liver uptake. We have explored trastuzumab fragment as a radio-theranostic agent. Trastuzumab Fab was generated using Papain enzyme tagged beads, incubation time 18 to 20 h at 850 rpm in phosphate buffer. Fab were collected with ultrafiltration device, cut off 30 kDa, in phosphate buffer pH 8. Quantification of Fab was done at 280 nm. Fab characterization was done using MALDI-TOF and SDS-PAGE. To enable radiolabelling of Fab with Ga-68 and Lu-177, Fab was conjugated with bifunctional chelator, DTPA. Fab-DTPA was separated by micro bio-spin P-6 chromatography columns and the average number of DTPA/Fab were calculated. Affinity of Fab conjugated Fab-DTPA for HER2 receptors was studied using the biolayer interferometry technique (BLI). Radiolabelling of Fab with Ga-68 for PET imaging and Lu-177 for therapy was optimized. Quality control included radiochemical purity using TLC in sodium citrate (pH 5) mobile phase, pyrogenicity using PTS, and sterility by tryptic soy broth culture media. Receptor affinity and apoptosis were studied with HER2 positive SKBR-3 cells using flow cytometry assay. The SKBR-3 cell (106) were cultured in 96 well plates and incubated with a known amount of Lu-177-DTPA-Fab (0- 18.5 MBq). First in human Ga-68 Fab PET/CT and Lu-177-Fab gamma camera images were acquired after obtaining clearance from Institutional Ethics Committee and inform signed consent. Patients were recruited with histopathological proven HER2 positive breast cancer and uptake on F-18 FDG PET/CT. Ga-68-DTPA-Fab (3.5-5 mCi) and 10-15 mCi Lu-177 DTPA-Fab was injected and images were acquired at 2/3 h and up to 7 days respectively. Dominant Fab peak at 45kDa on MALD-TOF, single band on SDS-PAGE (Non-reduced or reduced) have been obtained. Two DTPA/Fab were conjugated and confirmed by MALDI-TOF. BLI data showed Kd value of trastuzumab, Fab, and conjugated DTPA-Fab as 0.2 nM, 0.57 nM, and 20 nM for HER2. High labelling efficiency (≥98%) of Lu-177-DTPA-Fab and Ga-68-DTPA-Fab was achieved. Apoptosis (%) was 1.5%- 42.5% in SKBR-3 cells treated with Lu-177-DTPA-Fab. Both formulations were found sterile and pyrogen-free. Kidney and bladder activity of Ga-68/Lu-177-DTPA-Fab demonstrate renal clearance. Blood pool activity of both tracers were high. However, it was decreased, and lesion uptake was increased with time. All the lesions on Ga-68-DTPA-Fab, same as in F-18 FDG PET/CT, were picked up accept those near heart. Good lesion retention of Lu-177-DTPA-Fab was observed showing suitability for therapy. Fab-DTPA has potential to target HER2 receptor. It could be radiolabelled with Ga-68 for PET imaging and Lu-177 for targeted therapy. Citation Format: Jaya Shukla, Yogesh Rathore, Komalpreet Kaur, Santosh Irrinky, Rajender Kumar, Amanjit Bal, Bhagwant R Mittal. Radiolabelled Trastuzumab Fab as a theranostic agent for HER2 expressing breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B043.

Inflammatory activity of vulnerable plaques in asymptomatic, non-hemodynamically significant carotid artery stenoses: preliminary results of the carotid artery multi-modality imaging prognostic study

Abstract Background [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a valid technique to quantify carotid plaque inflammation and can improve identification of patients at high risk for stroke. There are few data on the inflammatory plaque activity in asymptomatic patients and of its association with other characteristics of plaque vulnerability. Purpose To assess the inflammatory carotid plaque activity and its correlations with patient characteristics and features of plaque vulnerability detected by other imaging techniques in a population of patients with asymptomatic mild/moderate degree of stenosis. Methods Seventy-five asymptomatic patients with 40-60% unilateral carotid stenosis at Doppler ultrasound (DUS) were prospectively evaluated with [18F]FDG-PET, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Regions of interests were drawn using fused PET/CT slices on the most diseased segment (MDS), defined as the single hottest slice of [18F]FDG uptake. Background blood pool activity was obtained from regions of interests placed in the lumen of the jugular vein. The target-to-background ratio (TBR) was calculated by dividing maximum standardized uptake value (SUVmax) of the MDS to SUVmax of ipsilateral blood pool activity. Plaque vulnerability was defined as the presence of an echolucent plaque at DUS, plaque ulceration at CTA, intraplaque hemorrhage, and lipid-rich necrotic core at MRA. Results Patients with a TBR ≥median (1.75), compared with those below the median, were significantly more frequently male and on statin therapy, had higher prevalence of ulcerated plaque at CTA (61% vs 35%, p=0.03) and intraplaque hemorrhage at MRA (33% vs 10%, p=0.03), while the prevalence of a lipid-rich necrotic core at MRA was not significantly different (p=0.16). TBR and SUVmax of the MDS were similar in those with or without a ≥50% stenosis, and peak velocities indices at DUS were not significantly correlated with TBR or SUVmax. Log(TBR) was significantly higher in ulcerated, rather than non-ulcerated, plaque (0.27 vs 0.21, p=0.03) and numerically higher in plaques with an intraplaque hemorrhage (0.22 vs 0.30, p=0.06). Log(TBR) and Log(SUVmax) were similar in plaques with and without a lipid-rich necrotic core (p=0.86 for both). Conclusions Higher TBR or SUVmax, indicating a high inflammatory activity, are associated with an ulcerated plaque and the presence of intraplaque hemorrhage but not with either the degree of stenosis or the presence of a lipid-rich necrotic core.

Myocardial fibrosis activity following ST-segment elevation myocardial infarction

Abstract Background Myocardial fibrosis following myocardial infarction (MI) is a key healing mechanism and involves widespread fibroblast activation. Once activated, fibroblasts express fibroblast activation protein (FAP) (1). Hybrid positron emission tomography (PET) imaging of radiolabelled fibroblast activation protein inhibitor (FAPI) fused with cardiovascular magnetic resonance (68Ga-FAPI PET/MR) is an emerging method for assessing myocardial fibrosis activity that may provide additional insights into the recovery of the heart following MI. Methods Forty patients with acute (&amp;lt;4 weeks), 19 with recent (12 weeks), and 19 with prior established ST-segment elevation MI (&amp;gt;12 months), and 20 healthy volunteer participants underwent 68Ga-FAPI PET/MR. Participants were imaged 30 min after administration of 100-200 MBq 68Ga-FAPI-04. Image analysis was performed using FusionQuant (Cedars Sinai, Los Angeles, California). 68Ga-FAPI uptake was quantified by maximum standardised uptake value (SUVmax) and tissue-to-background ratio (TBRmax) correcting for blood-pool activity in the left ventricle. Comparisons between were assessed with one-way ANOVA with Tukey-Kramer post-hoc testing where significant differences were detected. A 2-sided p-value of &amp;lt;0.05 denoted statistical significance. Results Participants were predominantly middle-aged men with similar sized infarcts (peak plasma cardiac troponin concentrations and post-MI left ventricular ejection fraction) (Table). Blood pool tracer activity was also similar between groups. Focal myocardial 68Ga-FAPI uptake localised to areas of the infarct and peri-infarct zones on magnetic resonance late gadolinium enhancement imaging (Figure). Both myocardial SUVmax and TBRmax varied between infarcts of different ages, being highest in acute (TBRmax 4.1±1.2) and lowest in those with prior established MI (2.1±0.7, Table and Figure). Conclusions Fibrosis activity is greatest in the immediate aftermath of acute MI with a step-wise reduction in the weeks and years that follow. Fibrosis activity continues for many months and years after acute infarction.FigureTable

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

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

Comparison of SUVA/V and SUVA-V for Evaluating Atherosclerotic Inflammation in 18F-FDG PET/CT.

This study aimed to compare the clinical significance of two parameters, division of standardized uptake value (SUV) of target arterial activity by background venous blood pool activity (SUVA/V) and subtraction of background venous blood pool activity from SUV of target arterial activity (SUVA-V) of carotid arteries with atherosclerotic plaques using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). Patients aged 50 years or more who were diagnosed with carotid artery stenosis of 50% or more with carotid Doppler ultrasonography and had torso 18F-FDG PET/CT were enrolled retrospectively and classified patients who developed cerebrovascular events (CVEs) within 5 years after 18F-FDG PET/CT scan as the active group and patients who did not experience the CVE within 5 years as an inactive group. We calculated SUVA/V and SUVA-V using measurements of SUVmax of carotid arteries and mean SUV of superior vena cava (SVC). SUVA-V, SUVA-V_high, and SUVA-V_low were significantly higher in the active group than in the inactive group, but neither SUVA/V, SUVA/V_high, nor SUVA/V_low showed significant differences between the active and inactive groups. The difference in rank between groups of SUVA/V_high and SUVA/V_low was greater than the difference in rank between groups of SUVA-V_high and SUVA-V_low. The CVE incidence differed between SUVA/V_high and SUVA/V_low of high carotid FDG uptake, but the CVE incidence did not differ between SUVA-V_high and SUVA-V_low of high carotid FDG uptake. SUVA-V may be a more rational solution than SUVA/V for evaluating atherosclerotic plaque inflammation on 18F-FDG PET/CT.

Diagnostic values of delayed additional FDG PET/CT scan in the evaluation of cardiac sarcoidosis.

This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scans in patients with cardiac sarcoidosis (CS). Twenty-three patients with CS (median age: 69years; 11 women) were retrospectively evaluated using dual-phase FDG PET/CT. All patients were instructed to consume a low-carbohydrate diet followed by fasting for 18h before FDG injection to reduce physiological myocardial uptake. PET/CT was acquired at 60min (early) and 100min (delayed) after FDG administration. Focal and focal on diffuse uptake on visual analysis was considered positive for CS. A semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) of the cardiac lesion and the mean SUV (SUVmean) of the blood pool. Significant myocardial FDG uptake was observed in 21 patients (91.3%) in the early acquisition group and in 23 patients in the delayed scan group (100%). Compared to the early scan, the delayed scan showed a significantly higher SUVmax of the cardiac lesion [median, 4.0; IQR (interquartile range, 2.9 to 7.0) vs. 5.8 (IQR 3.7 to 10.1); P = 0.0030] and a significantly lower SUVmean of blood pool [median, 1.3 (IQR, 1.2 to 1.4) vs. 1.1 (IQR, 0.9 to 1.2); P < 0.0001]. Delayed FDG PET/CT acquisition improves detection accuracy in patients with CS compared to early scans with washout of the blood pool activity. Therefore, it can contribute to a more accurate assessment of CS.

Time course of myocardial fibrosis activity following ST elevation myocardial infarction using 68Ga-FAPI PET/MR

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation - Prof Marc Dweck Senior Fellowship, and BHF Research Excellence Award 3 for Dr Anna K Barton. Background Myocardial fibrosis is a key healing response following myocardial infarction (MI). Although scar formation following MI is considered complete by 12 weeks, its exact time course is unknown. Fibroblast activation protein is a key factor in fibrogenesis that is expressed by activated fibroblasts in the myocardium following MI. Hybrid positron emission tomography and cardiovascular magnetic resonance (PET/MR) with radiolabelled fibroblast activation protein inhibitor (68Ga-FAPI) is an emerging method to measure in vivo fibrosis activity. Purpose To investigate the timing of myocardial fibrosis activity following ST-elevation MI using 68Ga-FAPI PET/MR Methods Twenty patients underwent multi-timepoint hybrid 68Ga-FAPI PET/MR &amp;lt;1, 2, 4, and 12 weeks following acute ST-elevation MI. They were compared to patients with prior established ST-elevation MI (&amp;gt;12 months) and healthy controls who underwent single-timepoint 68Ga-FAPI PET/MR to determine fibrosis activity in chronic infarcts and healthy myocardium respectively. All participants were imaged 30 min following administration of 100–200 MBq 68Ga-FAPI-04. Infarct zone 68Ga-FAPI uptake was quantified using tissue-to-background ratio (TBRmax) after correction for blood-pool activity in the left ventricle. Comparisons between timepoints for the acute MI group were assessed by ANOVA with repeated measures and post hoc Bonferroni correction, and between groups by two-tailed t-test. Results Participants were predominantly middle-aged men (Table). Focal 68Ga-FAPI uptake localised to areas of infarction within the infarct and peri-infarct zones on late gadolinium enhancement on magnetic resonance imaging (Figure). In acute MI, there was substantial uptake with consistent TBRmax values at weeks 1, 2 and 4 (Table and Figure). Though TBRmax values started to decline by week 12 they remained persistently elevated compared to prior established MI and healthy myocardium (Table). Participants with prior established MI had modestly increased 68Ga-FAPI uptake compared with the healthy myocardium of control participants (Table and Figure). Conclusions Intense myocardial fibrosis activity is observed in the infarct and peri-infarct zones throughout the first month following ST-elevation MI. Although this starts to decline by 12 weeks, it remains markedly elevated even several years after myocardial infarction, indicating that low-level chronic fibroblast activity is a feature of established MI.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Comparison of 1-h with 3-h planar 99mTc-pyrophosphate scintigraphy in patients with suspected transthyretin cardiac amyloidosis using SPECT as a reference standard.

The purpose of this study was to examine the diagnostic value of planar 99mTc-pyrophosphate (PYP) imaging at 1 and 3h after tracer administration in patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) using SPECT as a reference standard. We also tested whether blood pool activity of PYP is associated with renal dysfunction. PYP images of 109 consecutive patients with suspected ATTR-CA were retrospectively reviewed. The myocardial PYP uptake was visually graded on a scale of 0 to 3 and quantified with the heart-to-contralateral (H/CL) ratio in accordance with the current expert consensus recommendations. The diagnostic value of planar images for identifying positive PYP SPECT was assessed by a receiver-operating characteristic curve analysis with the area under the curve (AUC). The uptake ratios of the ascending and descending aorta, left atrium, and trapezius muscle divided by the liver uptake were measured on SPECT images and compared to the renal function. A total of 41 patients (38%) had myocardial PYP uptake on SPECT images. In comparison with the visual scores on 1-h anterior planar images, those on 3-h anterior planar images had lower sensitivity (80.5% vs. 97.6%) and higher specificity (86.8% vs. 55.9%) for identifying positive PYP SPECT. The ROC analysis showed that the combination of visual scores on both 1-h and 3-h anterior planar images had significantly higher AUC values in comparison with 1-h anterior planar images alone (0.90 [95% CI 0.83-0.94] vs. 0.83 [95% CI 0.75-0.88]; P < 0.001), which was comparable to the AUC values on 3-h anterior planar images alone (0.88 [95% CI 0.80-0.92]; P = 0.071). In comparison with visual scores on 1-h or 3-h anterior planar images alone, the combination of visual scores and H/CL ratio did not significantly improve the diagnostic value for identifying positive PYP SPECT (P = 0.73 and P = 0.50, respectively). The uptake ratios of ascending aorta/liver, descending aorta/liver, left atrium/liver, and trapezius muscle/liver were not significantly associated with the serum creatinine level or estimated glomerular filtration rate (P > 0.05 for all). In the assessment of ATTR-CA using PYP imaging, visual scores on 3-h anterior planar images for identifying positive PYP SPECT had lower sensitivity and higher specificity in comparison with those on 1-h anterior planar images. The diagnostic value of the visual scores on 1-h and 3-h anterior planar images was not improved by adding the H/CL ratio. Blood pool activity of PYP was not significantly associated with renal dysfunction.

TSPO expression in a Zika virus murine infection model as an imaging target for acute infection-induced neuroinflammation

IntroductionZika virus (ZIKV) is a neurotropic human pathogen that causes neuroinflammation, whose hallmark is elevated translocator protein (TSPO) expression in the brain. This study investigates ZIKV-associated changes in adult brain TSPO expression, evaluates the effectiveness of TSPO radioligands in detecting TSPO expression, and identifies cells that drive brain TSPO expression in a mouse infection model.MethodsThe interferon-deficient AG129 mouse infected with ZIKV was used as neuroinflammation model. TSPO expression was evaluated by tissue immunostaining. TSPO radioligands, [3H]PK11195 and [18F]FEPPA, were used for in vitro and ex vivo detection of TSPO in infected brains. [18F]FEPPA-PET was used for in vivo detection of TSPO expression. Cell subsets that contribute to TSPO expression were identified by flow cytometry.ResultsBrain TSPO expression increased with ZIKV disease severity. This increase was contributed by TSPO-positive microglia and infiltrating monocytes; and by influx of TSPO-expressing immune cells into the brain. [3H]PK11195 and [18F]FEPPA distinguish ZIKV-infected brains from normal controls in vitro and ex vivo. [18F]FEPPA brain uptake by PET imaging correlated with disease severity and neuroinflammation. However, TSPO expression by immune cells contributed to significant blood pool [18F]FEPPA activity which could confound [18F]FEPPA-PET imaging results.ConclusionsTSPO is a biologically relevant imaging target for ZIKV neuroinflammation. Brain [18F]FEPPA uptake can be a surrogate marker for ZIKV disease and may be a potential PET imaging marker for ZIKV-induced neuroinflammation. Future TSPO-PET/SPECT studies on viral neuroinflammation and related encephalitis should assess the contribution of immune cells on TSPO expression and employ appropriate image correction methods to subtract blood pool activity.

Imaging of post-infarct myocardial inflammation with 68Ga-DOTATATE PET/MRI

Abstract Background After myocardial infarction (MI), inflammation and its resolution modulate the extent of myocardial damage. 68Ga-DOTATATE is a PET tracer that binds to somatostatin receptor 2 (SST2), which is up-regulated in pro-inflammatory macrophages [1]. Purpose We investigated 68Ga-DOTATATE PET/MRI for quantifying post-infarct myocardial inflammation. Methods In this prospective observational cohort study, participants with MI underwent 68Ga-DOTATATE PET/MRI at baseline (t0: &amp;lt;2 weeks post-MI) and 3 months (t3M). Patients with prior MI, heart failure, coronary revascularisation, or contraindication to PET/MRI, were excluded. Blood samples were taken at the time of imaging for high sensitivity CRP (hsCRP), high sensitivity troponin I (hsTnI), NTproBNP and peripheral blood monocyte subset counts measured by mass cytometry. 68Ga-DOTATATE maximum Standardised Uptake Values (SUV) and Tissue-to-Background Ratios (TBR) adjusted for blood pool activity were compared in the infarct defined by late gadolinium enhancement (LGE) MRI to remote myocardium at t0 and t3M. Results Thirty-two patients (mean age 59 [SD 9] years; 26 [81%] male and 6 [19%] female), comprised of 18 (56%) patients with ST elevation MI and 14 (44%) with non-ST elevation MI, were enrolled. Mean peak troponin was 16,953ng/L (range 408 to &amp;gt;25,000ng/L), and 16 (52%) patients had left ventricular impairment (ejection fraction &amp;lt;50%). 68Ga-DOTATATE PET signal co-localised with myocardial LGE and focal oedema (arrows) on T2-weighted MRI (Fig. 1; asterisk: culprit artery) and had excellent ability to discriminate infarct from remote regions (t0: infarct SUV 2.41 vs. remote 1.58, p&amp;lt;0.0001; t0: infarct TBR 5.08 vs. 3.35, p&amp;lt;0.0001; Fig. 2a). At 100 (SD 13) days after MI (n=23 patients), residual 68Ga-DOTATATE uptake in the infarct remained higher than remote myocardium (t3M: infarct SUV 1.88 vs. remote 1.27, p&amp;lt;0.0001; t3M: infarct TBR 3.96 vs. remote 2.73, p&amp;lt;0.0001), but was reduced compared to baseline (SUV −22%, p&amp;lt;0.0001; TBR −22%, p=0.002; Fig. 2b). Reduction in infarct 68Ga-DOTATATE uptake was consistent with overall decreases in hsCRP (2.16 vs. 8.76 mg/L), hsTnI (19 vs. 1365 ng/L) and NTproBNP (372 vs. 959 pg/mL) at t3M vs. t0 (n=23, all p&amp;lt;0.05). Focal oedema on MRI was resolved in 17 (74%) patients at t3M. Infarct-to-remote TBR ratio at t0 was correlated with hsTnI (r=0.35, p&amp;lt;0.05). At t3M (n=9 samples) vs t0 (n=20 samples), there was a reduction in % classical-to-non-classical ratio of peripheral monocytes (mean 6.5 [SD 3.8] vs. 14.4 [SD 11.2], p=0.005). Conclusions This is the first prospective study of serial 68Ga-DOTATATE PET/MRI in patients after MI. Here we show that 68Ga-DOTATATE tracks resolving myocardial inflammation. Ongoing work as part of this study seeks to confirm the cellular origin of infarct-related 68Ga-DOTATATE PET signal and SST2 expression within inflamed myocardial tissue, and test its longer-term association with ischaemic myocardial remodelling. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome TrustBritish Heart Foundation