Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment paradigms yet simultaneously posed significant challenges due to various immune-related adverse events (irAEs). Among...Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment paradigms yet simultaneously posed significant challenges due to various immune-related adverse events (irAEs). Among these, ICI-associated myocarditis-a rare but potentially fatal complication that severely impacts long-term patient prognosis-makes early diagnosis and risk stratification crucial. However, its highly heterogeneous and insidiously progressive clinical presentation challenges timely and accurate detection by conventional diagnostic methods, highlighting an urgent clinical need for more effective approaches. Positron emission tomography (PET) molecular imaging, by targeting specific pathophysiological processes, holds great potential for non-invasive diagnosis and monitoring of this disease. Ongoing advances in novel probes and imaging technologies may further improve the capability of PET to characterize key mechanisms of ICI-associated myocarditis, providing a unique imaging window for early and precise intervention. Based on current clinical evidence and research findings, this article elaborates on the application value of PET molecular imaging in the clinical management of ICI-associated myocarditis and summarizes recent research progress, aiming to inform future clinical practice and investigation.
Cardiovascular diseases involve complex immune-associated biological processes that remain difficult to characterize using conventional imaging approaches. Although positron emission tomography (PET) has emerged as an im...Cardiovascular diseases involve complex immune-associated biological processes that remain difficult to characterize using conventional imaging approaches. Although positron emission tomography (PET) has emerged as an important molecular imaging modality in cardiology, current metabolic tracers often lack sufficient specificity and may be limited by nonspecific myocardial uptake. Immuno-PET, which combines antibody-based targeting agents with the sensitivity and quantitative capability of PET, offers a promising strategy for noninvasive characterization of cardiovascular biology. In this review, we discuss emerging immuno-PET targets relevant to cardiovascular disease, including pan-leukocyte, lymphocyte-associated, myeloid/macrophage-associated, and vascular activation markers. We additionally review key technical and translational considerations for cardiovascular immuno-PET, including probe design, tissue penetration, blood clearance, radionuclide selection, and target-to-background limitations. Together, recent advances in antibody engineering, nanobody development, radiochemistry, and immune-target discovery are rapidly expanding the potential of immuno-PET for precision imaging of cardiovascular disease.
O'Gorman KJ, Bremner L, Mian Z
… +21 more, Yang L, Shetty M, Cohen YA, Prasad M, Rosenblum HR, Hoffman MK, Bearelly S, Thakoor KA, Chou CJ, Park YJ, Castillo M, Johnson LL, DeLuca A, Kinkhabwala M, Liu Q, Chernovolenko M, Goldner K, Ciano A, Uriel N, Clerkin K, Einstein AJ
INTRODUCTION: Cardiac PET is an established tool for detecting cardiac allograft vasculopathy (CAV), however, transplant-patient-specific normal values for myocardial blood flow (MBF), myocardial blood flow reserve (MBFR...INTRODUCTION: Cardiac PET is an established tool for detecting cardiac allograft vasculopathy (CAV), however, transplant-patient-specific normal values for myocardial blood flow (MBF), myocardial blood flow reserve (MBFR), and left ventricular parameters are limited. We aimed to define normal ranges in heart transplant (HT) recipients using two software programs and to assess agreement between software-derived metrics. METHODS: We retrospectively evaluated 266 HT recipients undergoing N-ammonia PET between 2021-2023. Studies without ischemia or scar were included and compared with invasive coronary angiography and intravascular ultrasound. Normal values for MBF, MBFR, left ventricular volumes, and left ventricular ejection fraction were derived in patients without angiographic CAV and in a subset without micro-intimal disease, using two different software programs, Invia-4DM and Cedars-Sinai. Agreement between software-derived metrics was assessed using correlation and Bland-Altman analyses. RESULTS: Ninety-three patients without angiographic CAV (56 without micro-intimal disease) met criteria for normal reference value derivation. Rate-pressure-product-correction had a significant influence on the MBFR, with lower limits of normal for uncorrected MBFR and rate-pressure-product-corrected-MBFR ranging between 1.80-2.04 and 2.10-2.37, respectively, depending on the software program and use of residual subtraction. Values of software-derived metrics demonstrated strong monotonic relationship and moderate-to-good absolute agreement but the intraclass correlation coefficient was <0.90 for most metrics and there were wide limits of agreement for MBF metrics. CONCLUSION: This study establishes software-specific normal reference values for N-ammonia PET metrics in HT recipients without CAV. These findings support the use of software-specific thresholds and consistent post-processing for longitudinal assessment in transplant populations.
BACKGROUND: A global myocardial flow reserve (MFR) threshold of 2.5 is clinically used to define normal vasodilatory capacity with O-water PET myocardial perfusion imaging but lacks prognostic validation. Since mean glob...BACKGROUND: A global myocardial flow reserve (MFR) threshold of 2.5 is clinically used to define normal vasodilatory capacity with O-water PET myocardial perfusion imaging but lacks prognostic validation. Since mean global MFR exceeds 3.5 in healthy individuals, the 2.5-3.5 range may represent an intermediate-risk "gray zone". We aimed to evaluate a 4-tiered global MFR categorization for risk stratification. METHODS: We retrospectively included patients with known or suspected chronic coronary syndromes who underwent clinically indicated O-water PET. Patients were stratified into four groups by global MFR: >3.5, 2.5-3.5, 1.5-<2.5, and <1.5. Major adverse cardiac events (MACE) were defined as all-cause death or hospitalization for acute myocardial infarction, unstable angina, or acute heart failure. Prognostic value was evaluated using Cox hazard ratios (HR [95% confidence interval]). RESULTS: Among 783 consecutive patients (median age 68; 45% female), 129 MACE occurred over a median follow-up of 3.5 years. Patients with MFR >3.5 (n=204) exhibited an annualized MACE rate of 0.6 per 100 person-years, with no MACE occurring during the first 2.5 years. MFR 2.5-3.5 (n=310) had a 5-fold higher annualized MACE rate (3.1 per 100 person-years; HR 5.4[2.3-13]), increasing to 6.8 for MFR 1.5-<2.5 (n=201; HR 12[5.1-28]) and 13.7 for MFR <1.5 (n=68; HR 24[10-59]). Group differences remained significant after multivariable adjustment (P ≤ 0.029). CONCLUSIONS: Risk of MACE increases progressively with declining global MFR. We propose a 4-tiered categorization of MFR for reporting risk, using MFR >3.5 to indicate a low-risk profile.
Katahira M, Fukushima K, Ikeda A
… +12 more, Kasahara S, Ukon N, Kawakubo M, Yamakuni R, Kiko T, Yamamoto A, Shimizu T, Ishii S, Oikawa M, Nagao M, Ito H, Takeishi Y
UNLABELLED: Positron emission tomography (PET) provides robust assessment of cardiac function, whereas evaluation of the right ventricle (RV) remains challenging. Myocardial strain analysis has emerged as a sensitive mar...UNLABELLED: Positron emission tomography (PET) provides robust assessment of cardiac function, whereas evaluation of the right ventricle (RV) remains challenging. Myocardial strain analysis has emerged as a sensitive marker for subtle wall dysfunction. We aimed to evaluate the feasibility of RV strain quantification using a newly developed PET feature tracking technique, with magnetic resonance (MR) strain as the reference standard. METHODS: Consecutive 123 patients (mean 68 ys, male 101) who underwent rest N ammonia PETMR were retrospectively enrolled. Semi-automatic PET feature tracking was performed using previously validated in-house MATLAB-based software. RV global longitudinal (GLS %) and circumferential strain (GCS %) were derived from 4-chamber and short-axis gated PET cine images, respectively. For comparison, reference values were quantified from simultaneously acquired breath-hold cine MR using commercially available software. RESULTS: Mean GLS and GCS were -24.1±6.9% vs. -23.4±5.6% and -16.2±5.4% vs. -16.6±4.2% for PET and CMR, respectively. Both parameters showed strong correlations between the two modalities (r=0.77 and 0.74 for GLS and GCS, respectively; p<0.0001). Bland-Altman analysis demonstrated acceptable agreement, despite the presence of significant proportional bias (GLS: bias 0.1±4.4% [limits of agreement (LOA) -8.6 to 8.8], r=0.2, and p=0.01; GCS: bias -0.7±3.6% [LOA -7.8 to 6.4], r=-0.4, and p<0.0001, respectively). CONCLUSION: PET derived RV wall strain analysis demonstrated a significant correlation with MR strain. PET feature tracking has the potential as a useful tool to detect RV wall dysfunction in routine clinical practice.
OBJECTIVE: To describe the rationale and design of the multicenter phase 3 Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) trial evaluating the diagnostic performance of I-evuzamitide positron emis...OBJECTIVE: To describe the rationale and design of the multicenter phase 3 Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) trial evaluating the diagnostic performance of I-evuzamitide positron emission tomography/computed tomography (PET/CT) for detection of cardiac amyloidosis (CA) in patients undergoing evaluation for suspected disease. BACKGROUND: I-evuzamitide is a novel fibril-targeting positron emitting radiotracer that binds hypersulfated heparan sulfate glycans in amyloid fibrils across multiple amyloid subtypes. METHODS: This open-label, single-arm study, enrolled adults with suspected CA at 18 U.S. CENTERS: Participants with previously diagnosed CA or systemic amyloidosis with known organ involvement, precursor protein targeted therapy use, estimated glomerular filtration rate < 15 mL/min/1.73 m, recent myocardial infarction or recent heparin exposure were excluded. Cardiac and partial-body static PET/CT imaging was performed 4 ± 1 hours after intravenous administration of I-evuzamitide (1.0 ± 0.1 mCi). Potassium iodide was administered to reduce thyroid uptake of free radioiodine. Three blinded expert physicians independently assessed myocardial tracer uptake visually on PET/CT scans. Separately, three blinded amyloidosis experts adjudicated the presence or absence of CA, using standard-of-care clinical, laboratory, biopsy, genetic, electrocardiographic, echocardiographic, cardiac magnetic resonance, and bone-avid tracer cardiac scintigraphy data. The primary endpoints are sensitivity and specificity of visually interpreted I-evuzamitide PET/CT for diagnosis of CA compared with adjudicated standard-of- care diagnosis. CONCLUSIONS: REVEAL is the first multicenter phase 3 study evaluating a fibril-targeted PET radiotracer for diagnosis of CA and may establish a non-invasive molecular imaging approach for detecting cardiac and systemic amyloid deposition across multiple amyloid subtypes.
BACKGROUND: Myocardial flow reserve (MFR) reflects the ability of the coronary circulation to augment blood flow in response to increased demand, integrating both epicardial and microvascular function. Although its progn...BACKGROUND: Myocardial flow reserve (MFR) reflects the ability of the coronary circulation to augment blood flow in response to increased demand, integrating both epicardial and microvascular function. Although its prognostic value has been demonstrated with invasive techniques and positron emission tomography (PET), evidence using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) remains limited. The aim of this study was to evaluate the prognostic impact of MFR assessed by CZT-SPECT in patients with and without obstructive coronary artery disease (CAD). METHODS: We retrospectively analyzed 452 consecutive patients who underwent one-day rest/stress ˆ99mTc-sestamibi dynamic CZT-SPECT for MFR quantification. MFR was calculated as the ratio of stress to rest myocardial blood flow, with values <2 considered abnormal. Median follow-up was 792 days. Follow-up was censored at the last documented clinical visit for patients without events. Adverse cardiovascular events included angina, myocardial infarction, stroke, revascularization, hospitalization for angina or heart failure, and death. Major adverse cardiovascular events (MACE) were defined as death, myocardial infarction, revascularization, or stroke. Kaplan-Meier survival curves and Cox proportional hazard models were used, and incremental prognostic value was assessed with the C-index and likelihood ratio tests. RESULTS: Among 452 patients (mean age: 63 ± 12 years, 54% male), 190 (42%) had MFR <2. During follow-up, 190 total events and 63 major events occurred. All deaths (n = 7) were observed in the reduced MFR group. MFR <2 was significantly associated with a higher risk of total events (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 2.5-5.7; P < 0.001) and major events (HR: 7.9, 95% CI: 3.5-17.6; P < 0.001). Incorporating MFR improved predictive performance (C-index from 0.63 to 0.77 for total events and from 0.76 to 0.84 for MACE; both P < 0.001). CONCLUSIONS: MFR <2 assessed by CZT-SPECT significantly predicted adverse cardiovascular outcomes, including death, and provided incremental prognostic value beyond clinical risk factors and relative perfusion imaging. Routine incorporation of MFR assessment may improve risk stratification and guide personalized management of chronic coronary syndromes.
BACKGROUND: Previously published effective dose coefficient estimates for O-water are around 1 μSv/MBq, resulting in an effective dose of around 0.4 mSv for a typically injected activity of 400 MBq in clinical cardiac sc...BACKGROUND: Previously published effective dose coefficient estimates for O-water are around 1 μSv/MBq, resulting in an effective dose of around 0.4 mSv for a typically injected activity of 400 MBq in clinical cardiac scans. These estimates were based on limited positron emission tomography (PET) information combined with pharmacokinetic models. Large-axial field-of-view (LAFOV) PET allows for dynamic scanning of all relevant organs in a single scan and hence should result in more accurate dosimetry estimates. The aim of the present work was to estimate radiation dosimetry of O-water based on dynamic LAFOV PET. METHODS: Ten patients underwent 4 minutes 40 seconds dynamic PET scans after automated bolus injection of 350 ± 27 MBq O-water on a Quadra LAFOV PET scanner (Siemens Healthineers) at Turku PET Centre. All organs with visual uptake over background were segmented and time-activity curves were calculated and uncorrected for decay. Time-integrated activity coefficients (TIACs) were calculated by rectangular integration followed by exponential extrapolation. The remainder of the body TIAC was calculated as the theoretical maximum TIAC minus the sum of all source organs. Organ absorbed doses were calculated using IDAC-DOSE 2.1 and effective dose was estimated according to ICRP 103. RESULTS: The highest TIACs were found in the lungs, liver, and brain, whereas the highest absorbed dose was found in heart wall, spleen, and kidneys. The sex-averaged effective dose coefficient was 0.62 ± 0.09 (mean ± standard deviation) μSv/MBq. CONCLUSION: The effective dose of O-water is considerably lower than previously published values, amounting to an effective dose of approximately 0.25 mSv for a typical cardiac scan.
BACKGROUND: Right ventricular (RV) failure is the primary determinant of prognosis in pulmonary hypertension (PH) and is associated with metabolic remodeling. However, the relationship between RV metabolic activity, pulm...BACKGROUND: Right ventricular (RV) failure is the primary determinant of prognosis in pulmonary hypertension (PH) and is associated with metabolic remodeling. However, the relationship between RV metabolic activity, pulmonary vascular load, and right ventricular-pulmonary arterial (RV-PA) coupling remains incompletely understood. We hypothesized that increased pulmonary vascular afterload is associated with enhanced RV glucose metabolism and impaired RV-PA coupling, reflecting early maladaptive RV adaptation before overt structural remodeling develops. This study investigated the interplay among pulmonary vascular resistance (PVR), RV structure, RV-PA coupling, and RV myocardial glucose metabolism using integrated cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Fifty patients with pre-capillary PH underwent CMR and FDG-PET. Ventricular volumes were quantified by CMR, and RV-PA coupling was estimated using the stroke volume-to-end-systolic volume ratio (SV/ESV). RV metabolic activity was quantified using standardized uptake value (SUV). Associations among PVR, RV structure, RV-PA coupling, and RV metabolic activity were analyzed. RESULTS: PVR was positively correlated with SUV RV (r = 0.452, P < 0.001), indicating increased RV glucose uptake with higher afterload. PVR was inversely correlated with SV/ESV (r = -0.282, P = 0.048), indicating impaired RV-PA coupling. Right ventricular end-diastolic volume index showed a modest association with SUV RV (r = 0.273, P = 0.055) and was not significantly correlated with SV/ESV (r = -0.197, P = 0.170). These findings indicate that RV metabolic remodeling is more closely associated with pulmonary vascular afterload and RV-PA uncoupling than with overt RV dilatation. CONCLUSIONS: RV glucose metabolism is significantly associated with pulmonary vascular load and impaired RV-PA coupling, potentially reflecting early maladaptive adaptation to increased afterload preceding overt structural remodeling. Integrated FDG-PET and CMR assessment provides complementary mechanistic insights into RV adaptation in PH.