18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

Preclinical Four-Dimensional Functional Lung Imaging and Quantification of Regional Airflow: A New Standard in Lung Function Evaluation in Murine Models.

The current standard for lung function evaluation in murine models is based on forced oscillation technology, which provides a measure of the total airway function but cannot provide information on regional heterogeneity in function. Limited detection of regional airflow may contribute to a discontinuity between airway inflammation and airflow obstruction in models of asthma. Here, we describe quantification of regional airway function using novel dynamic quantitative imaging and analysis to quantify and visualize lung motion and regional pulmonary airflow in four dimensions (4D). Furthermore, temporo-spatial specific ventilation (ml/ml) is used to determine ventilation heterogeneity indices for lobar and sublobar regions, which are directly compared to ex vivo biological analyses in the same sublobar regions. In contrast, oscillation-based technology in murine genetic models of asthma have failed to demonstrate lung function change despite altered inflammation, whereas 4D functional lung imaging demonstrated diminished regional lung function in genetic models relative to wild-type mice. Quantitative functional lung imaging assists in localizing the regional effects of airflow. Our approach reveals repeatable and consistent differences in regional airflow between lung lobes in all models of asthma, suggesting that asthma is characterized by regional airway dysfunctions that are often not detectable in composite measures of lung function. 4D functional lung imaging technology has the potential to transform discovery and development in murine models by mapping out regional areas heterogeneously affected by the disease, thus deciphering pathobiology with greater precision.

Computational approaches to detect small lesions in 18 F-FDG PET/CT scans.

PURPOSE: When physicians interpret 18 F-FDG PET/CT scans, they rely on their subjective visual impression of the presence of small lesions, the criteria for which may vary among readers. Our investigation used physical phantom scans to evaluate whether image texture analysis metrics reliably correspond to visual criteria used to identify lesions and accurately differentiate background regions from sub-centimeter simulated lesions. METHODS: Routinely collected quality assurance test data were processed retrospectively for 65 different 18 F-FDG PET scans performed of standardized phantoms on eight different PET/CT systems. Phantoms included 8-, 12-, 16-, and 25-mm diameter cylinders embedded in a cylindrical water bath, prepared with 2.5:1 activity-to-background ratio emulating typical whole-body PET protocols. Voxel values in cylinder regions and background regions were sampled to compute several classes of image metrics. Two experienced physicists, blinded to quantified image metrics and to each other's readings, independently graded cylinder visibility on a 5-level scale (0 = definitely not visible to 4 = definitely visible). RESULTS: The three largest cylinders were visible in 100% of cases with a mean visibility score of 3.3 ± 1.2, while the smallest 8-mm cylinder was visible in 58% of cases with a significantly lower mean visibility score of 1.5±1.1 (P < 0.0001). By ROC analysis, the polynomial-fit signal-to-noise ratio was the most accurate at discriminating 8-mm cylinders from the background, with accuracy greater than visual detection (93% ± 2% versus 76% ± 4%, P = 0.0001), and better sensitivity (94% versus 58%, P < 0.0001). CONCLUSION: Image texture analysis metrics are more sensitive than visual impressions for detecting sub-centimeter simulated lesions. Therefore, image texture analysis metrics are potentially clinically useful for 18 F-FDG PET/CT studies.

Loss of dihydrotestosterone-inactivation activity promotes prostate cancer castration resistance detectable by functional imaging.

Androgens such as testosterone and dihydrotestosterone are a critical driver of prostate cancer progression. Cancer resistance to androgen deprivation therapies ensues when tumors engage metabolic processes that produce sustained androgen levels in the tissue. However, the molecular mechanisms involved in this resistance process are unclear, and functional imaging modalities that predict impending resistance are lacking. Here, using the human LNCaP and C4-2 cell line models of prostate cancer, we show that castration treatment-sensitive prostate cancer cells that normally have an intact glucuronidation pathway that rapidly conjugates and inactivates dihydrotestosterone and thereby limits androgen signaling, become glucuronidation deficient and resistant to androgen deprivation. Mechanistically, using CRISPR/Cas9-mediated gene ablation, we found that loss of UDP glucuronosyltransferase family 2 member B15 (UGT2B15) and UGT2B17 is sufficient to restore free dihydrotestosterone, sustained androgen signaling, and development of castration resistance. Furthermore, loss of glucuronidation enzymatic activity was also detectable with a nonsteroid glucuronidation substrate. Of note, glucuronidation-incompetent cells and the resultant loss of intracellular conjugated dihydrotestosterone were detectable in vivo by 18F-dihydrotestosterone PET. Together, these findings couple a mechanism with a functional imaging modality to identify impending castration resistance in prostate cancers.

Do myocardial PET-MR and PET-CT FDG images provide comparable information?

INTRODUCTION: Although positron emission tomography PET-MR imaging is emerging into clinical practice, many aspects of this imaging technique such as attenuation correction have yet to be validated for myocardial imaging. Thus, it is uncertain whether PET-MR FDG images provide clinical information which is comparable to PET-CT FDG images. The study goal was to systematically compare relative myocardial FDG concentrations obtained from cardiac PET-MR images to those derived from same day PET-CT images. METHODS: Myocardial FDG images of 27 patients undergoing PET-CT imaging, followed by PET-MR imaging 42 ± 13 minutes later as part of a prospective oncology study were analyzed. Mean segmental standardized uptake measurements (SUVmean) were obtained in each of the 17 standard myocardial segments and normalized to the brightest segment. RESULTS: Normalized segmental SUVmean values did not differ significantly between the PET-MR and PET-CT images (mean difference 0.002, P = .826). The specific segment was a marginally significant predictor of the differences (P = .057), with the largest difference in the anteroseptal basal segment. CONCLUSIONS: PET-MR, vis-à-vis PET-CT, does not significantly raise segmental uptake relative to the brightest segment, suggesting that PET-MR can be used similarly to PET-CT for applications where relative uptake is important.

Improving the biodistribution of PSMA-targeting tracers with a highly negatively charged linker.

BACKGROUND: Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer and in tumor vasculature. Small molecule based inhibitors of PSMA have promised to provide sensitive detection of primary and metastatic prostate tumors. Although significant progress has been made, many of the radiolabeled imaging agents exhibit non-specific background binding. Prevailing tracer designs focus on high affinity urea-based inhibitors with strategically placed hydrophobic patches that interact favorably with the substrate tunnel of PSMA. We hypothesized that a novel PSMA inhibitor design incorporating highly negatively charged linkers may minimize non-specific binding and decrease overall background. METHODS: Through iterative redesign, we generated a series of PSMA inhibitors with highly negatively charged linkers that connect to urea inhibitors and bulky radionuclide chelates. We then performed in vivo imaging and biodistribution studies with the radiolabeled tracers. RESULTS: The tracers derived from our iterative redesign have affinities for PSMA comparable to the "parent" urea ligand Cys-C(O)-Glu. Using a fluorine-18 labeled PSMA targeting tracer, we found that these highly negatively charged molecules exhibit rapid renal excretion with minimal non-specific binding. The biodistribution data at 2 hr showed 4.6%ID/g PC3-PIP tumor uptake with spleen, liver, bone, and blood background levels of 0.1%, 0.17%, 0.1%, and 0.04%, respectively. CONCLUSION: Placement of multiple negative charges in the linker region of PSMA tracers significantly reduced the non-specific background binding without significant reduction of binding affinity. This increased tumor/background contrast in positron emission tomography promises to provide more sensitive tumor detection while decreasing the overall radiation exposure to patients.

A novel PSMA-targeting tracer with highly negatively charged linker demonstrates decreased salivary gland uptake in mice compared to [68Ga]Ga-PSMA-11.

BACKGROUND: The current generation of radiolabeled PSMA-targeting therapeutic agents is limited by prominent salivary gland binding, which results in dose-limiting xerostomia from radiation exposure. JB-1498 is a urea-based small molecule with a highly negatively charged linker targeting prostate specific membrane antigen (PSMA). Prior work on a similar tracer with the same negatively charged linker demonstrated low normal organ/soft tissue background uptake compared to [68Ga]Ga-PSMA-11. The purpose of this study was to investigate if [68Ga]Ga-JB-1498 had reduced salivary gland uptake in mice compared to [68Ga]Ga-PSMA-11. RESULTS: JB-1498 demonstrated high affinity for PSMA binding and tumor uptake in a murine tumor model. In an initial biodistribution study with low molar activity, [68Ga]Ga-JB-1498 demonstrated salivary gland uptake of 0.13 ± 0.01%ID/g. In a second biodistribution study in non-tumor-bearing mice with high molar activity, [68Ga]Ga-JB1498 demonstrated salivary gland uptake of 0.39 ± 0.24% ID/g and kidney activity of 10.12 ± 1.73% ID/g at one hour post IV injection. This salivary gland uptake is significantly less than the published uptake of [68Ga]Ga-PSMA-11. Micro-PET visually confirmed the findings of the biodistribution studies. Dynamic micro-PET imaging demonstrated gradually decreasing [68Ga]Ga-JB1498 activity in salivary glands and kidneys, compared to gradually increasing [68Ga]Ga-PSMA-11 activity in these two organs during the first hour. CONCLUSION: Biodistribution and micro-PET imaging of [68Ga]Ga-JB-1498 demonstrate significantly decreased salivary gland uptake and different pharmacokinetic behavior in kidneys and salivary glands in mice compared to [68Ga]Ga-PSMA-11. Our findings suggest that constructing a PSMA-targeting molecule with a highly negatively charged linker is a promising strategy to reduce salivary gland uptake of GCP-II/PSMA ligands in theranostic applications.

A Perspective on Protein Structure Prediction Using Quantum Computers.

Despite the recent advancements by deep learning methods such as AlphaFold2, in silico protein structure prediction remains a challenging problem in biomedical research. With the rapid evolution of quantum computing, it is natural to ask whether quantum computers can offer some meaningful benefits for approaching this problem. Yet, identifying specific problem instances amenable to quantum advantage and estimating the quantum resources required are equally challenging tasks. Here, we share our perspective on how to create a framework for systematically selecting protein structure prediction problems that are amenable for quantum advantage, and estimate quantum resources for such problems on a utility-scale quantum computer. As a proof-of-concept, we validate our problem selection framework by accurately predicting the structure of a catalytic loop of the Zika Virus NS3 Helicase, on quantum hardware.

Prospective comparison of positron emission tomography (PET)/magnetic resonance and PET/computed tomography dosimetry in hepatic malignant neoplastic disease after 90Y radioembolization treatment.

Background: 90Y radioembolization is an established treatment modality for hepatic malignancies. Successful radioembolization requires optimal dose delivery to tumors while minimizing dosages to parenchyma. Post-treatment positron emission tomography (PET)/computed tomography (CT) dosimetry is the established benchmark, whereas PET/magnetic resonance (MR) is an emerging modality. The goal of this study was to assess the intermodality agreement between PET/MR and PET/CT 90Y dosimetry. Methods: In this single-institution study, 18 patients (20 treatment sessions) with a primary or metastatic hepatic malignancy underwent both PET/MR and PET/CT after 90Y radioembolization. Patients were randomized to undergo one modality first, followed by the other. The region of interest was delineated using MR images and tumor and liver dosimetry was calculated. Intermodality agreement was assessed using the Bland-Altman method. A generalized linear model was used to assess the effect of baseline variables on intermodality dose differences. Results: PET/MR underestimated tumor and liver absorbed doses when compared to PET/CT by -3.7% (P=0.042) and -5.8% (P=0.029), respectively. A coverage probability plot demonstrated that 80% and 90% of tumor dose measurements fell within intermodality differences of 11% and 18%, respectively. PET/MR underestimated tumor dose at both low (<1 GBq) and high (>3 GBq) injected activity levels (P<0.001) by -22.3 [standard deviation (SD) =13.5] and -24.3 (SD =18.7), respectively. Conclusions: Although PET/MR significantly underestimated the absorbed dose when compared to PET/CT, the intermodality agreement was high and the degree of underestimation was better than previously reported. Intermodality differences were more pronounced at low and high injected doses. Additional studies are required to assess the clinical implications of these findings.

Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension.

Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH. Methods: We enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined. Results: Individuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL, p<0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain (R=-0.43, p=0.02 and R=-0.37, p=0.05 respectively), RV fractional area change (R=0.51, p<0.01 and R=0.48, p<0.01 respectively), RV end-systolic area (R=-0.63, p<0.001 and R=-0.48, p<0.01 respectively), RV end-diastolic area: R=-0.58, p<0.001 and R=-0.41, p=0.03 respectively), and RV glucose uptake by PET (R=-0.46, p=0.01 and R=-0.30, p=0.10 respectively). NT-proBNP was negatively correlated with TC (R=-0.61, p=0.01) and TG (R=-0.62, p<0.02) in PH. Conclusion: These findings confirm dyslipidemia is associated with worse right ventricular function in PH.

Novel Depiction of Collateral Flow in Chronic Thromboembolic Pulmonary Hypertension Using 4D Dynamic 82 Rb PET/CT.

ABSTRACT: CT pulmonary angiogram and ventilation-perfusion scintigraphy are the 2 primary imaging modalities for evaluating patients with CTEPH (chronic thromboembolic pulmonary hypertension). PET/CT and MRI currently have a limited role in the evaluation of acute or chronic pulmonary embolism. We present incidentally captured dynamic pulmonary perfusion images in a patient with history of CTEPH who underwent 82 Rb myocardial perfusion PET/CT for evaluation of chest pain. Analysis of the PET data revealed delayed perfusion of the affected lobes suggesting collateralization, highlighting a potentially new imaging paradigm for assessment of pulmonary perfusion.

CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma.

T cell lymphomas (TCL) are heterogeneous, aggressive, and have few available targeted therapeutics. In this study, we determined that CD6, an established T cell marker, was expressed at high levels on almost all examined TCL patient specimens, suggesting that CD6 could be a new therapeutic target for this life-threatening blood cancer. We prepared a CD6-targeted antibody-drug conjugate (CD6-ADC) by conjugating monomethyl auristatin E (MMAE), an FDA-approved mitotic toxin, to a high-affinity anti-human CD6 monoclonal antibody (mAb). In contrast to both the unconjugated anti-CD6 mAb, and the non-binding control ADC, CD6-ADC potently and selectively killed TCL cells in vitro in both time- and concentration-dependent manners. It also prevented the development of tumors in vivo in a preclinical model of TCL. More importantly, systemic or local administration of the CD6-ADC or its humanized version, but not the controls, significantly shrank established tumors in the preclinical mouse model of TCL. These results suggest that CD6 is a novel therapeutic target in TCLs and provide a strong rationale for the further development of CD6-ADC as a promising therapy for patients with these potentially fatal lymphoid neoplasms.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Small-animal imaging using clinical positron emission tomography/computed tomography and super-resolution.

Considering the high cost of dedicated small-animal positron emission tomography/computed tomography (PET/CT), an acceptable alternative in many situations might be clinical PET/CT. However, spatial resolution and image quality are of concern. The utility of clinical PET/CT for small-animal research and image quality improvements from super-resolution (spatial subsampling) were investigated. National Electrical Manufacturers Association (NEMA) NU 4 phantom and mouse data were acquired with a clinical PET/CT scanner, as both conventional static and stepped scans. Static scans were reconstructed with and without point spread function (PSF) modeling. Stepped images were postprocessed with iterative deconvolution to produce super-resolution images. Image quality was markedly improved using the super-resolution technique, avoiding certain artifacts produced by PSF modeling. The 2 mm rod of the NU 4 phantom was visualized with high contrast, and the major structures of the mouse were well resolved. Although not a perfect substitute for a state-of-the-art small-animal PET/CT scanner, a clinical PET/CT scanner with super-resolution produces acceptable small-animal image quality for many preclinical research studies.

Effect of stress testing on left ventricular mechanical synchrony by phase analysis of gated positron emission tomography in patients with normal myocardial perfusion.

PURPOSE: There are limited data on whether differences exist in left ventricular (LV) mechanical dyssynchrony indices derived from stress versus rest gated positron emission tomography (PET) in patients with normal myocardial perfusion imaging (MPI). METHODS: Stress/rest (82)Rb gated PET was performed in consecutive patients with normal MPI between 2006 and 2010. Patients were divided into two groups: group 1 [LV ejection fraction (EF) ≥ 55% and QRS < 120 ms] and group 2 (LVEF ≤35%). Images were acquired on a dedicated PET scanner prior to and on a hybrid PET/CT system after November 2008. LV dyssynchrony indices [phase standard deviation (SD)° and SD (ms)] were derived from stress and rest gated images. RESULTS: There were 91 patients in group 1 (age 61 ± 13, LVEF 66 ± 8%, normal QRS) and 126 in group 2 (age 66 ± 12, LVEF 25 ± 7%). The stress derived LVEF were significantly higher than rest for either group (p < 0.0001). Patients with cardiomyopathy had significantly higher dyssynchrony indices compared to those with normal LVEF (rest SD° 49.2 ± 21.5° vs 16.8 ± 7.8° and stress SD° 42.5 ± 19.4° vs 12.4 ± 3.7°, respectively, p < 0.0001 for both). The dyssynchrony indices derived from rest gated images were significantly higher than those derived from stress in both groups (p < 0.001 by unpaired and paired t test) and irrespective of the type of PET scanner utilized. Finally, 20/87 (23%) patients with normal LVEF and 27/66 (41%) of those with cardiomyopathy but without dyssynchrony based on stress indices were recategorized as having significant dyssynchrony given their resting indices. CONCLUSION: LV mechanical dyssynchrony indices by phase analysis are smaller when derived from peak stress versus rest gated PET imaging in patients with normal MPI, irrespective of the resting LVEF.

Comparison and validation of automated scoring of SPECT phantom cold rod visibility.

PURPOSE: Evaluation of phantom image quality is an integral component of the quality assurance of SPECT systems. This evaluation often is done by visual assessment of the resolution of known structures of a specified size, such as arrays of cold rods in a warm background. Although this method is rapid and convenient, it is qualitative and is subject to inter- and intraobserver variability. Thus an automated quantitative analysis would be preferable. Several metrics of cold rod visibility have been developed, although their suitability for SPECT quality assurance depends on how well they correspond to visual scoring by experienced observers. METHODS: Various metrics of cold rod visibility, derived from either texture analysis or template-based analysis, were investigated. The texture analysis methods measured the normalized gray-level co-occurrence matrix (GLCM) energy ("Energy%") and entropy ("Entropy%") of each region and an associated combination of the two ("EnergyEntropy%"). One template-based method measured the rods-to-background contrast ("Contrast") and an associated visibility index (Contrast × area = "Contrast Visibility"). Another template-based method performed binary classification (BC) of the rods and background to compute the area under curve (AUC) of its receiver operating characteristics (ROC) curve ("BC-AUC") and the corresponding signal-to-noise ratio ("BC-SNR"). All these metrics were computed for 90 SPECT acquisitions of the standard American College of Radiology ("Jaszczak") phantom. Cold rod visibility was scored independently by two experienced nuclear medicine physicists on both dichotomous and 5-point scales. Scoring was performed twice by each observer to evaluate variability. RESULTS: Interobserver agreement (Cohen's kappa statistic) was 0.78, and intraobserver reproducibility was 0.86 and 0.88, respectively, for each observer. Mean and median scores differed significantly between observers. Accuracy of each metric was assessed according to AUC of ROC analysis with respect to mean dichotomous score. The binary classification metrics had the highest accuracy (BC-AUC = 0.995, BC-SNR = 0.994), above that of the texture analysis metrics (Entropy% = 0.992, Energy% = 0.988, EnergyEntropy% = 0.992) and conventional template analysis (Contrast = 0.984, Contrast Visibility = 0.989). The metrics were similar in terms of rank correlation to mean visibility score. BC-AUC correlated linearly with mean visibility score (R2  = 0.95) and consistently performed among the highest of the metrics vs rod diameter and count level. CONCLUSIONS: Automated quantitative analysis of SPECT phantom cold rods correlated well with visual scoring. The metrics based on binary classification performed particularly well for this task, across the range of rod diameters and count levels. The suboptimal interobserver agreement highlights the importance of developing automated algorithms for evaluating scanner performance.

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis.

Background: Cardiac amyloidosis is an increasingly recognized etiology of heart failure, in part due to the rise of non-invasive nuclear bone scintigraphy. Molecular imaging using positron emission tomography (PET) has promised the direct visualization of cardiac amyloid fibrils. We sought to assess the performance of F18-florbetapir PET in patients with a potential for cardiac amyloidosis in order to identify early disease. Methods: We performed a pilot study of 12 patients: one with asymptomatic transthyretin cardiac amyloidosis, seven with a potential for developing cardiac amyloidosis (two smoldering myeloma and five with extracardiac biopsy demonstrating transthyretin amyloid deposits and negative technetium pyrophosphate scans), and four controls. Patients were imaged with PET/CT in listmode 10-20 min after receiving F18-florbetapir. Static images were created from this acquisition, and mean standardized uptake values (SUVs) of the left ventricular myocardium, blood pool, paraspinal muscles, and liver were calculated. Results: All 12 patients demonstrated radiotracer uptake in the myocardium with mean SUV of 2.3 ± 0.4 and blood pool SUV of 0.8 ± 0.1. The patient with cardiac amyloidosis had SUV of 3.3, while mean SUV for patients at risk was 2.3 ± 0.4 and for controls was 2.2 ± 0.3. After 3 years of follow-up, one patient with SUV below the mean was subsequently diagnosed with ATTR cardiac amyloidosis. Conclusion: In this cohort, PET with F18-florbetapir demonstrated non-specific radiotracer uptake in the myocardium in all patients using a static image protocol; though, the highest values were noted in a patient with ATTR cardiac amyloidosis. There was no difference in the intensity of F18-florbetapir uptake in at-risk patients and controls. Future studies should continue to investigate metabolic PET tracers and protocols in cardiac amyloidosis, including in early disease.