Rupture prone high-risk atheromatous plaques are characterized by large necrotic core volumes covered by thin fibrous caps which are positively remodeled; these plaques are significantly inflamed by the cells of monocyte-macrophage origin. We propose that the development of a position-sensitive positron-counting catheter, adding directionality with lead shields (sCath), would help record quantitative location-specific uptake of specifically targeted radiotracers against inflammation. For in-vitro study, the catheter was placed on 18F point sources to measure the radioactivity counts. For ex-vivo study, the 9 aortas dissected from the rabbit model of atherosclerosis were exposed, and catheters were pulled back every 1 cm and counts measured the for 1 min by non-shielded catheter (nsCath), sCath-R (right side) and sCath-L (left side). In-vitro study showed linear correlation between counts and 18F point source dose until at least 100 kBq (r = 0.98, p < 0.0001). In ex-vivo study, total 100 sections were obtained from 9 aortas and counts-per-minute (cpm) from each catheter nsCath, sCath-R, -L and the average of sCath-R and -L demonstrated high correlation coefficients with quantitative

The small molecule radiotracer 124I-PU-H71 is an imaging biomarker of epichaperome formation. The tracer has been established to localize in tissues under chronic stress, specifically in cancer cells and neurodegenerative brain cells. A first-in-human imaging trial using positron emission tomography (PET) in cancer patients revealed unexpected tracer accumulation in the myocardium. To describe human 124I-PU-H71 myocardial biodistribution and pharmacokinetics in a series of cancer patients with no history of cardiovascular disease. 25 cancer patients (age 22–75 years, M:F − 7:18) with no history of cardiovascular disease received intravenous injections with microdose 124I-PU-H71 while at rest, followed by dynamic and gated/non-gated PET image data acquisitions. Region-of-interest (ROI) analysis of left ventricular myocardium (LVmyo) and background left atrium quantified tracer concentrations as standardized uptake value (SUV) and uptake ratios. Kinetic rate constants were evaluated by a two-tissue compartment model. Myocardial accumulation of 124I-PU-H71 was prominent in all patients, with median LVmyo SUVmean (interquartile range, IQR) of 2.8 (IQR, 2.13–3.29), 2.5 (IQR, 1.94–2.98), 2.4 (IQR, 1.73–3.31) and 1.0 (IQR, 0.61–2.45), and median LVmyo/blood-pool ratios of 1.9 (IQR, 1.57–2.38), 2.0 (IQR, 1.53–2.32), 3.6 (IQR, 2.91–4.06) and 3.9 (IQR, 2.62–5.08) at 1–9 min, 14–23 min, 3–4 h and 21–25 h, respectively on non-gated PET images. Myocardium showed peak uptake within 2 min post-injection, with sustained myocardial tracer-concentration at 4 h post-injection. Pharmacokinetic modeling revealed median K1 = 0.45 ml/min/g (IQR, 0.38–0.62); k2 = 0.47 min− 1 (IQR, 0.27–0.71); k3 = 0.16 min− 1 (IQR, 0.09–0.26); and k4 = 0.0038 min− 1 (IQR, 0.0015–0.0057). Regional assessment demonstrated essentially uniform tracer uptake in LV and myocardial segments; with normal LVEF in all patients (mean 57.7 ± 3.5

Atherosclerotic plaques progress as a result of inflammation. Both invasive and noninvasive imaging techniques have been developed to identify and characterize plaque as vulnerable (more likely to rupture and cause a clinical event). Imaging techniques to identify vulnerable include identifying vessels with focal subendothelial collections of I) inflammatory cells; II) lipid/ fatty acid; III) local regions of hypoxia; IV) local expression of angiogenesis factors; V) local expression of protease; VI) intravascular foci of thrombus; hemorrhage (most often seen in the aftermath of a clinical event); VII) apoptosis and VIII) microcalcification. This review provides an overview of atherosclerotic plaque progression and tracers which can visualize specific molecules associated with vulnerability.

Nipah virus (NiV) infection, often fatal in humans, is primarily transmitted in Bangladesh through the consumption of date palm sap contaminated by Pteropus bats. Person-to-person transmission is also common and increases the concern of large outbreaks. This study aimed to characterize the molecular epidemiology, phylogenetic relationship, and the evolution of the nucleocapsid gene (N gene) of NiV.We conducted molecular detection, genetic characterization, and Bayesian time-scale evolution analyses of NiV using pooled Pteropid bat roost urine samples from an outbreak area in 2012 and archived RNA samples from NiV case patients identified during 2012–2018 in Bangladesh.NiV-RNA was detected in 19% (38/456) of bat roost urine samples and among them; nine N gene sequences were recovered. We also retrieved sequences from 53% (21 out of 39) of archived RNA samples from patients. Phylogenetic analysis revealed that all Bangladeshi strains belonged to NiV-BD genotype and had an evolutionary rate of 4.64 × 10−4 substitutions/site/year. The analyses suggested that the strains of NiV-BD genotype diverged during 1995 and formed two sublineages.This analysis provides further evidence that the NiV strains of the Malaysian and Bangladesh genotypes diverged recently and continue to evolve. More extensive surveillance of NiV in bats and human will be helpful to explore strain diversity and virulence potential to infect humans through direct or person-to-person virus transmission.

Background Patients who developed myocarditis following SARS-CoV-2 vaccination show abnormalities on cardiac MRI. However, whether myocardial changes occur in asymptomatic individuals following vaccination is not well established. Purpose To assess myocardial 18Fluorine-fluorodeoxyglucose (18F-FDG) uptake on PET/CT in asymptomatic SARS-CoV-2 vaccinated patients compared to nonvaccinated patients. Materials and Methods This retrospective study included patients who underwent 18F-FDG PET/CT for indications unrelated to myocarditis during the period before (11/1/2020 - 2/16/2021) and after (2/17/20121 - 3/31/2022) SARS-CoV-2 vaccines were available. Myocardial and axillary FDG uptake were quantitatively assessed using maximum standardized uptake value (SUVmax). SUVmax values in all patients and in patients stratified by sex (male/female), age (<40, 41-60, >60 years), and time interval between vaccination and PET/CT were compared using Mann-Whitney U test or Kruskal-Wallis test with post ad -hoc Dwass, Steel, Critchlow-Fligner multiple comparison analysis. Results The study included 303 nonvaccinated patients (mean age, 52.9 years ± 14.9 [SD]; 157 females) and 700 vaccinated patients (mean age, 56.8 years ± 13.7 [SD]; 344 females). Vaccinated patients had overall higher myocardial FDG uptake compared to nonvaccinated patients (median SUVmax, 4.8 [IQR: 3.0-8.5] vs median SUVmax, 3.3 [IQR: 2.5-6.2]; P < .0001). Myocardial SUVmax was higher in vaccinated patients regardless of sex (median range, 4.7-4.9 [IQR: 2.9-8.6]) or patient age (median range, 4.7-5.6 [IQR: 2.9-8.6]) compared to corresponding nonvaccinated groups (sex median range, 3.2-3.9 [IQR: 2.4-7.2]; age median range, 3.3-3.3 [IQR: 2.3-6.1]; P range, <.001-.015). Furthermore, increased myocardial FDG uptake was observed in patients imaged 1-30, 31-60, 61-120, and 121-180 days after their second vaccination (median SUVmax range, 4.6-5.1 [IQR: 2.9-8.6]) and increased ipsilateral axillary uptake was observed in patients imaged 1-30, 31-60, 61-120 days after their 2nd vaccination (median SUVmax range, 1.5-2.0 [IQR: 1.2-3.4]) compared to the nonvaccinated patients (P range, <.001-<.001). Conclusion Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT. See also the editorial by Bluemke in this issue.

Myocardial flow reserve (MFR), derived from quantitative measurements of myocardial blood flow during PET imaging, provides prognostic information on patients with coronary artery disease (CAD), but it is not known if this also applies to cancer patients with a competing risk for mortality. Methods: To determine the prognostic value of MFR in patients with cancer, we designed a retrospective cohort study comprising 221 patients with known or suspected CAD (median age, 71 y; range, 41-92 y) enrolled between June 2009 and January 2011. Most patients were referred for perioperative risk assessment. Patients underwent measurement of myocardial blood flow at rest and during pharmacologic stress, using quantitative 82Rb PET imaging. They were divided into early-stage versus advanced-stage cancer groups based on cancer histopathology and clinical state and were further stratified by myocardial perfusion summed stress score, summed difference score, and calculated MFR. Overall survival (OS) was assessed using the Kaplan-Meier estimator, and Cox proportional-hazards regression helped identify independent predictors for OS. Results: During a follow-up of 85.6 mo, 120 deaths occurred. MFR, summed difference score, and cancer stage were significantly associated with OS. In the age-adjusted Cox hazard multivariable analysis, MFR and cancer stage remained independent prognostic factors. MFR combined with cancer stage enhanced OS discrimination. The groups had significantly different outcomes (P < 0.001), with 5-y OS of 88% (MFR ≥ 1.97 and early-stage), 53% (MFR < 1.97 and early-stage), 33% (MFR ≥ 1.97 and advanced-stage), and 13% (MFR < 1.97 and advanced-stage). Conclusion: Independent of cancer stage, MFR derived from quantitative PET was prognostic of OS in our cohort of cancer patients with known or suspected CAD. Combining these 2 parameters enhanced discrimination of OS, suggesting that MFR improves risk stratification and may serve as a treatment target to increase survival in cancer patients.

here are 3 types of fat in the human body: white, brown, and beige ( 1 ). White adipocytes deposit extra energy into triglycerides, whereas beige and brown adipocytes have the unique ability to convert mitochondrial energy into heat (rather than adenosine triphosphate) via uncoupling protein 1. Obesity, especially excess fat in tissue that is normally lean, increases the risk of cardiovascular disease ( 2 ). In addition to the amount of fat, the distribution of fat, especially increased abdominal fat, evaluated by the ratio of waist to hip circumfer-ences, predicts glucose intolerance, insulin resistance, hyperten-sion, and hypertriglyceridemia ( 3,4 ). PET/CT with 18 F-FDG provides a unique opportunity to view the metabolic activity of brown adipose tissue (BAT). However, even though visceral and subcutaneous fat are substantially less metabolically active than BAT, both are metabolically active tissues ( 5 ). Visceral adipose tissue is more metabolically active than subcutaneous fat. BAT is a thermoregulatory organ that consumes stored energy to produce heat through the expression of uncoupling protein 1. This phenomenon is called nonshivering thermogenesis and plays an important role in glucose and lipid metabolism ( 6 ). It is particularly intense in newborns, in whom it helps to maintain a

Part 2 of this series of Continuing Education articles on benign thyroid disorders deals with nodular goiter, hypothyroidism, and subacute thyroiditis. Together with Part 1 (which dealt with various forms of hyperthyroidism), this article is intended to provide relevant information for specialists in nuclear medicine dealing with the clinical management of patients with benign thyroid disorders, the primary audience for this series. Goiter, an enlargement of the thyroid gland, is a common endocrine abnormality. Constitutional factors, genetic abnormalities, or dietary and environmental factors may contribute to the development of nodular goiter. Most patients with nontoxic nodular goiter are asymptomatic or have only mild mechanical symptoms (globus pharyngis). Work-up of these patients includes measurement of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid autoantibodies, ultrasound imaging, thyroid scintigraphy, and fine-needle aspiration biopsy of nodules with certain ultrasound and scintigraphic features. Treatment for multinodular goiter includes dietary iodine supplementation, surgery, radioiodine therapy (to decrease thyroid size), and minimally invasive ablation techniques. Hypothyroidism ranges from rare cases of myxedema to more common mild forms (subclinical hypothyroidism). Primary hypothyroidism often has an autoimmune etiology. Clinical presentations differ in neonates, children, adults, and elderly patients. Work-up includes thyroid function tests and ultrasound imaging. Nuclear medicine is primarily used to locate ectopic thyroid tissue in congenital hypothyroidism or to detect defects in iodine organification with the perchlorate discharge test. Treatment consists of thyroid replacement therapy with l-thyroxine, adjusting the daily dose to the individual patient's metabolic and hormonal requirements. Subacute thyroiditis is a self-limited inflammatory disorder of the thyroid gland, often associated with painless or painful swelling of the gland and somatic signs or symptoms. Inflammation disrupts thyroid follicles resulting in a rapid release of stored thyroxine and triiodothyronine causing an initial thyrotoxic phase, often followed by transient or permanent hypothyroidism. Although subacute thyroiditis is often related to a viral infection, no infective agent has been identified. Subacute thyroiditis may be caused by a viral infection in genetically predisposed individuals. Work-up includes lab tests, ultrasound imaging, and radionuclide imaging. Thyroid scintigraphy demonstrates different findings depending on the phase of the illness, ranging from very low or absent tracer uptake in the thyroid gland in the hyperthyroid phase to a normal appearance in the late recovery phase. Since subacute thyroiditis is self-limited, treatment is directed toward relief of pain. High-dose nonsteroidal antiinflammatory drugs are usually the first-line treatment. If severe pain persists, a course of corticosteroids may be necessary. Permanent hypothyroidism develops in up to 15% of patients with subacute thyroiditis, even more than 1 y after presentation.

Background . Current lipid-lowering drugs often leave significant residual risk for adverse outcomes. Identification of previously approved drugs for new indications, drug repurposing, may provide a cost effective alternative to de novo drug developing. Objectives . We combined clinical, transcriptomic, computational, and experimental strategies to explore lipid-lowering and plaque-stabilizing effects of atypical antidepressant trazodone. Methods . First, a connectivity mapping strategy was used to match rosuvastatin gene expression signature derived from a clinical trial of 85 patients with to the expression patterns of 1,309 different small molecules to discover a similarity between the rosuvastatin and trazodone gene expression signatures. Then, we assessed the lipid-lowering ability of trazodone in vitro using HepG2 cells and in vivo using molecular imaging of rabbit atherosclerotic lesions. In addition, we analyzed electronic medical records of patients from three large medical centers who had a prescription for trazodone and lipid laboratory measurements available. Results . Trazodone significantly reduced cholesterol levels in the HepG2 human hepatocyte model, decreased atherosclerotic plaque burden in a rabbit model and lowered low-density lipoprotein (LDL) cholesterol levels in patients. Conclusion . Our results indicate that trazodone may be a promising candidate for adjunctive lipid lowering therapy. It may provide significant benefits to patients with hyperlipidemia, including lipid level reduction and formation of a more favorable atherosclerotic plaque morphology. Patients diagnosed with major depressive disorder requiring better lipid control would benefit the most from the for adjunctive lipid lowering therapy.

> We are not going to be the first to this party, but we are going to be the best. > > —Steve Jobs The initial tracer used to study bone metabolism ([1][1],[2][2]) was the artificially produced radionuclide 32P. The tracer, made as described in the note below, was fed orally to rats. The tracer

In the 1980s, Tl scintigraphy helped to introduce noninvasive assessment of myocardial perfusion as an important clinical tool for the detection and management of coronary artery disease (CAD). Monovalent cations such as Tl exhibit pharmacokinetics that are very suitable for the assessment of regional myocardial perfusion. Early uptake based on a high fi rst-pass extraction fraction of the radioisotope correlates linearly with myocardial blood fl ow over a wide fl ow range, allowing the sensitive detection of impaired coronary fl ow reserve. At later time points, the tracer washes out differentially, producing a redistribution pattern that has experimentally and clinically been linked to myocardial tissue viability. Therefore, the use of one tracer such as Tl has successfully addressed several clinical questions in patients with acute and chronic CAD and has established nuclear cardiology as a subspecialty of both nuclear medicine and cardiology (1). However, Tl has drawbacks due to its low photon energy. Image quality is less than optimal, which was especially appreciated as nuclear cardiology moved to SPECT. In addition, the long physical half-life of Tl is associated with a relatively high radiation exposure, which was further aggravated by the technique of reinjection as a means to enhance the redistribution process for the detection of regional tissue viability (2). For this reason, the advent of Tc-labeled blood fl ow tracers was very much welcomed by the nuclear cardiology community. Initial animal studies, however, showed that the physiologic characteristics in terms of fi rst-pass extraction fraction were less optimal than those of Tl (3). But the higher photon energy and the ease of preparation by commercially available Tc generators and kits overcame these limitations. First clinical experience showed that the diagnostic accuracy to detect regional CAD was quite comparable to that of Tl imaging (4). Since Tc-sestamibi does not redistribute, imaging can be performed for a long period after tracer injection, still refl ecting blood fl ow distribution at the time of injection. This slow redistribution has been exploited for assessment of patients with acute myocardial infarction, leading to measurement of infarct Received Jun. 11, 2020; revision accepted Jun. 15, 2020. For correspondence or reprints contact: Markus Schwaiger, Technical University of Munich, Ismaningerstrasse 22, Munich, 806275 Germany. E-mail: markus.schwaiger@tum.de COPYRIGHT © 2020 by the Society of Nuclear Medicine and Molecular Imaging. DOI: 10.2967/jnumed.120.251439

1380 Background: Statin use is not infrequently limited by side effects and often their maximum doses fall short of target cholesterol reduction. In a recent differential gene expression signature for rosuvastatin therapy composed of 117 genes, statistical comparison of expression patterns of MCF7 cell lines treated with 1309 small molecules predicted 9 matching compounds, of which dietary supplement, β Aescin ranked #2. Methods: We studied Aescin’s (active ingredient of horse chestnut seed extract, HCSE) ability to reduce experimentally-induced atherosclerosis in a 5-month high cholesterol diet rabbit model. Animals received pure Aescin, HCSE, or HCSE combined with Atorvastatin; controls were fed high cholesterol diet only. 99mTc-labeled Duramycin, a marker of inflammation and cell death, was used for molecular imaging; quantitative aorta Duramycin uptake was assessed as %injected dose/gram. Results: For this 25-rabbit study, a hierarchical Bayesian regression model was used to analyze differences in duramycin uptake. Relative to control, Duramycin uptake was lower by 12.5% (Asecin), 12.5% (HCSE) and 37.5% (HCSE + Statin) (Figure). HCSE + statin reduced uptake with >99% probability; Aescin (91% reduction probability, Bayes factor 10.3) and HCSE (88%, 7.2) alone may also reduce duramycin uptake. Conclusion: Working on the similar genetic pathways, dietary supplementation of Aescin or HCSE show trend to reduce cell death in atherosclerotic lesions and might help plaque stabilization.

Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with 99mTc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or 131I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the 131I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.

> We are not going to be the first to this party, but we are going to be the best. > > —Steve Jobs The initial tracer used to study bone metabolism ([1][1],[2][2]) was the artificially produced radionuclide 32P. The tracer, made as described in the note below, was fed orally to rats. The tracer