The discovery and evaluation of [18F]BMS-986229, a novel macrocyclic peptide PET radioligand for the measurement of PD-L1 expression and in-vivo PD-L1 target engagement.

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.

Association between Conversion to Shockable Rhythms and Survival with Favorable Neurological Outcomes for Out-of-Hospital Cardiac Arrests.

BACKGROUND: The initial cardiac rhythm in out-of-hospital cardiac arrest (OHCA) portends different prognoses and affects treatment decisions. Initial shockable rhythms are associated with good survival and neurological outcomes but there is conflicting evidence for those who initially present with non-shockable rhythms. The aim of this study is to evaluate if OHCA with conversion from non-shockable (i.e., asystole and pulseless electrical activity) rhythms to shockable rhythms compared to OHCA remaining in non-shockable rhythms is associated with better survival and neurological outcomes. METHOD: OHCA cases from the Pan-Asian Resuscitation Outcomes Study registry in 13 countries between January 2009 and February 2018 were retrospectively analyzed. Cases with missing initial rhythms, age <18 years, presumed non-medical cause of arrest, and not conveyed by emergency medical services were excluded. Multivariable logistic regression analysis was performed to evaluate the relationship between initial and subsequent shockable rhythm, survival to discharge, and survival with favorable neurological outcomes (cerebral performance category 1 or 2). RESULTS: Of the 116,387 cases included. 11,153 (9.6%) had initial shockable rhythms and 9,765 (8.4%) subsequently converted to shockable rhythms. Japan had the lowest proportion of OHCA patients with initial shockable rhythms (7.3%). For OHCA with initial shockable rhythm, the adjusted odds ratios (aOR) for survival and good neurological outcomes were 8.11 (95% confidence interval [CI] 7.62-8.63) and 15.4 (95%CI 14.1-16.8) respectively. For OHCA that converted from initial non-shockable to shockable rhythms, the aORs for survival and good neurological outcomes were 1.23 (95%CI 1.10-1.37) and 1.61 (95%CI 1.35-1.91) respectively. The aORs for survival and good neurological outcomes were 1.48 (95%CI 1.22-1.79) and 1.92 (95%CI 1.3 - 2.84) respectively for initial asystole, while the aOR for survival in initial pulseless electrical activity patients was 0.83 (95%CI 0.71-0.98). Prehospital adrenaline administration had the highest aOR (2.05, 95%CI 1.93-2.18) for conversion to shockable rhythm. CONCLUSION: In this ambidirectional cohort study, conversion from non-shockable to shockable rhythm was associated with improved survival and neurologic outcomes compared to rhythms that continued to be non-shockable. Continued advanced resuscitation may be beneficial for OHCA with subsequent conversion to shockable rhythms.

Evaluation of a PEGylated Fibroblast Growth Factor 21 Variant Using Novel Preclinical Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Mouse Model of Nonalcoholic Steatohepatitis.

BACKGROUND: Treatments for nonalcoholic steatohepatitis (NASH) are urgently needed. Hepatic fat fraction and shear stiffness quantified by magnetic resonance imaging (MRI-HFF) and magnetic resonance elastography (MRE-SS), respectively, are biomarkers for hepatic steatosis and fibrosis. PURPOSE: This study assessed the longitudinal effects of fibroblast growth factor 21 variant (polyethylene glycol [PEG]-FGF21v) on MRI-HFF and MRE-SS in a NASH mouse model. STUDY TYPE: Preclinical. ANIMAL MODEL: This study included a choline-deficient, amino acid-defined, high-fat diet (CDAHFD) model and 6-week-old, male C57BL/6J mice (N = 78). FIELD STRENGTH/SEQUENCE: This study was performed using: 3T: gradient-echo two-point Dixon and spin-echo (SE) echo-planar imaging elastography (200 Hz) and 7T: SE two-point Dixon and SE elastography (200 Hz). ASSESSMENT: MRI and MRE were performed before control diet (CD) or CDAHFD (BD), before PEG-FGF21v dosing (baseline), and after PEG-FGF21v treatment (WK4/8). Regions of interest for MRI-HFF and MRE-SS were delineated by J.L. and H.T. (>5 years of experience each). Fibrosis and steatosis were measured histologically after picrosirius red and H&E staining. Alkaline phosphatase, alanine transaminase, bile acids, and triglycerides (TGs) were measured. STATISTICAL TESTS: Two-tailed Dunnett's tests were used for statistical analysis; untreated CDAHFD or baseline was used for comparisons. Imaging and histology/biochemistry data were determined using Spearman correlations. Bayesian posterior distributions for MRE-SS at WK8, posterior means, and 95% credible intervals were presented. RESULTS: CDAHFD significantly increased baseline MRI-HFF (3T: 21.97% ± 0.29%; 7T: 40.12% ± 0.35%) and MRE-SS (3T: 1.25 ± 0.02; 7T: 1.78 ± 0.06 kPa) vs. CD (3T: 3.45% ± 0.7%; 7T: 12.06% ± 1.4% and 3T: 1.01 ± 0.02; 7T: 0.89 ± 0.06 kPa). At 7T, PEG-FGF21v significantly decreased MRI-HFF (WK4: 28.97% ± 1.22%; WK8: 20.93% ± 1.15%) and MRE-SS (WK4: 1.57 ± 0.04; WK8: 1.36 ± 0.05 kPa) vs. untreated (WK4: 36.36% ± 0.62%; WK8: 30.58% ± 0.81% and WK4: 2.03 ± 0.06; WK8: 2.01 ± 0.04 kPa); 3T trends were similar. WK8 SS posterior mean percent attenuation ratios (RDI ) were -68% (-90%, -44%; 3T) and -64% (-78%, -52%; 7T). MRI-HFF was significantly correlated with H&E (3T, r = 0.93; 7T, r = 0.94) and TGs (both, r = 0.92). DATA CONCLUSIONS: MRI-HFF and MRE-SS showed PEG-FGF21v effects on hepatic steatosis and fibrosis across 3 and 7T, consistent with histological and biochemical data. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Radiosynthesis and preclinical PET evaluation of 89Zr-nivolumab (BMS-936558) in healthy non-human primates.

Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types. This study reports the preparation and in vivo evaluation of 89Zr labeled nivolumab in healthy non-human primates (NHP) as a preliminary study of biodistribution and clearance. The radiochemical and in vivo stabilities of the 89Zr complex were shown to be acceptable for imaging. Three naïve NHPs were intravenously injected with tracer only or tracer co-injected with nivolumab followed by co-registered by positron emission tomography (PET) and magnetic resonance imaging (MRI), acquired for eight days following injection. Image-derived standardized uptake values (SUV) were quantified by region of interest (ROI) analysis. Radioactivity in the spleen was significantly reduced by addition of excess nivolumab compared to the tracer only study at all imaging time points. Liver uptake of the radiotracer was consistent as a clearance organ with minimal signal from other tissues: lung, muscle, brain, heart, and kidney. The results indicate specific biodistribution to the spleen, which can be blocked by co-administration of excess nivolumab. Distribution to other organs is consistent with elimination pathways of antibodies, with primary clearance through the liver.

Development, Characterization, and Radiation Dosimetry Studies of 18F-BMS-986229, a 18F-Labeled PD-L1 Macrocyclic Peptide PET Tracer.

PURPOSE: In cancer immunotherapy, the blockade of the interaction between programmed death-1 and its ligand (PD-1:PD-L1) has proven to be one of the most promising strategies. However, as mechanisms of resistance to PD-1/PD-L1 inhibition include variability in tumor cell PD-L1 expression in addition to standard tumor biopsy PD-L1 immunohistochemistry (IHC), a comprehensive and quantitative approach for measuring PD-L1 expression is required. Herein, we report the development and characterization of an 18F-PD-L1-binding macrocyclic peptide as a PET tracer for the comprehensive evaluation of tumor PD-L1 expression in cancer patients. PROCEDURES: 18F-BMS-986229 was characterized for PD-L1 expression assessment by autoradiography or PET imaging. 18F-BMS-986229 was utilized to evaluate tumor PD-L1 target engagement in competition with a macrocyclic peptide inhibitor of PD-L1 (BMS-986189) over a range of doses using PET imaging. A whole-body radiation dosimetry study of 18F-BMS-986229 in healthy non-human primates (NHPs) was performed. RESULTS: In vitro autoradiography showed an 8:1 binding ratio in L2987(PD-L1 +) vs. HT-29 (PD-L1-) tumors, more than 90% of which could be blocked with 1 nM of BMS-986189. Ex vivo autoradiography showed that 18F-BMS-986229 detection was penetrant over a series of sections spanning the entire L2987 tumor. In vivo PET imaging in mice demonstrated a 5:1 tracer uptake ratio (at 90-100 min after tracer administration) in L2987 vs. HT-29 tumors and demonstrated 83%-93% specific binding of BMS-986189 within those dose ranges. In a healthy NHP dosimetry study, the resultant whole-body effective dose was 0.025 mSv/MBq. CONCLUSION: 18F-BMS-986229 has been preclinically characterized and exhibits high target specificity, low background uptake, and a short blood half-life supportive of same day imaging in the clinic. As the PET tracer, 18F-BMS-986229 shows promise in the quantification of PD-L1 expression, and its use in monitoring longitudinal changes in patients may provide insights into PD-1:PD-L1 immuno-therapy treatment outcomes.

Multimodality rodent imaging chambers for use under barrier conditions with gas anesthesia.

PURPOSE: The ability to reproducibly and repeatedly image rodents in noninvasive imaging systems, such as small-animal positron emission tomography (PET) and computed tomography (CT), requires a reliable method for anesthetizing, positioning, and heating animals in a simple reproducible manner. In this paper, we demonstrate that mice and rats can be reproducibly and repeatedly imaged using an imaging chamber designed to be rigidly mounted on multiple imaging systems. PROCEDURES: Mouse and rat imaging chambers were made of acrylic plastic and aluminum. MicroCT scans were used to evaluate the positioning reproducibility of the chambers in multimodality and longitudinal imaging studies. The ability of the chambers to maintain mouse and rat body temperatures while anesthetized with gas anesthesia was also evaluated. RESULTS: Both the mouse and rat imaging chambers were able to reproducibly position the animals in the imaging systems with a small degree of error. Placement of the mouse in the mouse imaging chamber resulted in a mean distance of 0.23 mm per reference point in multimodality studies, whereas for longitudinal studies the mean difference was 1.11 mm. The rat chamber resulted in a mean difference of 0.46 mm in multimodality studies and a mean difference of 4.31 mm in longitudinal studies per reference point. The chambers maintained rodent body temperatures at the set point temperature of 38 degrees C. CONCLUSIONS: The rodent imaging chambers were able to reproducibly position rodents in tomographs with a small degree of variability and were compatible with routine use. The embedded anesthetic line and heating system was capable of maintaining the rodent's temperature and anesthetic state, thereby enhancing rodent health and improving data collection reliability.

Mapping the central effects of (±)-ketamine and traxoprodil using pharmacological magnetic resonance imaging in awake rats.

Major depressive disorder is a leading cause of disability globally. Improvements in the efficacy of antidepressant therapy are needed as a high proportion (>40%) of individuals with major depressive disorder fail to respond adequately to current treatments. The non-selective N-methyl-D-aspartate receptor channel blocker, (±)-ketamine, has been reported to produce a rapid and long-lasting antidepressant response in treatment-resistant major depressive disorder patients, which provides a unique opportunity for investigation of mechanisms that mediate its therapeutic effect. Efforts have also focused on the development of selective N-methyl-D-aspartate receptor subtype 2B antagonists which may retain antidepressant activity but have lower potential for dissociative/psychotomimetic effects. In the present study, we examined the central nervous system effects of acute, intravenous administration of (±)-ketamine or the N-methyl-D-aspartate receptor subtype 2B antagonist, traxoprodil, in awake rats using pharmacological magnetic resonance imaging. The study contained five treatment groups: vehicle, 3 mg/kg (±)-ketamine, and three doses of traxoprodil (0.3 mg/kg, 5 mg/kg, and 15 mg/kg). Non-linear model fitting was performed on the temporal hemodynamic pharmacological magnetic resonance imaging data to generate brain activation maps as well as regional responses based on blood oxygen level dependent signal changes for group analysis. Traxoprodil at 5 mg/kg and 15 mg/kg produced a dose-dependent pharmacological magnetic resonance imaging signal in rat forebrain regions with both doses achieving >80% N-methyl-D-aspartate receptor subtype 2B occupancy determined by ex vivo [3H]Ro 25-6981 binding. The middle dose of traxoprodil (5 mg/kg) generated region-specific activations in medial prefrontal cortex, ventral orbital cortex, and anterior cingulate cortex whereas the high dose (15 mg/kg) produced a widespread pharmacological magnetic resonance imaging response in both cortical and subcortical brain regions which was similar to that produced by (±)-ketamine (3 mg/kg, intravenous).

Synthesis and Biologic Evaluation of a Novel 18F-Labeled Adnectin as a PET Radioligand for Imaging PD-L1 Expression.

The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status in primary and metastatic lesions could be important for optimizing drug therapy. Herein, we have evaluated the tumor targeting of an anti-PD-L1 adnectin after 18F-fluorine labeling. Methods: An anti-PD-L1 adnectin was labeled with 18F in 2 steps. This synthesis featured fluorination of a novel prosthetic group, followed by a copper-free click conjugation to a modified adnectin to generate 18F-BMS-986192. 18F-BMS-986192 was evaluated in tumors using in vitro autoradiography and PET with mice bearing bilateral PD-L1-negative (PD-L1(-)) and PD-L1-positive (PD-L1(+)) subcutaneous tumors. 18F-BMS-986192 was evaluated for distribution, binding, and radiation dosimetry in a healthy cynomolgus monkey. Results:18F-BMS-986192 bound to human and cynomolgus PD-L1 with a dissociation constant of less than 35 pM, as measured by surface plasmon resonance. This adnectin was labeled with 18F to yield a PET radioligand for assessing PD-L1 expression in vivo. 18F-BMS-986192 bound to tumor tissues as a function of PD-L1 expression determined by immunohistochemistry. Radioligand binding was blocked in a dose-dependent manner. In vivo PET imaging clearly visualized PD-L1 expression in mice implanted with PD-L1(+), L2987 xenograft tumors. Two hours after dosing, a 3.5-fold-higher uptake (2.41 ± 0.29 vs. 0.82 ± 0.11 percentage injected dose per gram, P < 0.0001) was observed in L2987 than in control HT-29 (PD-L1(-)) tumors. Coadministration of 3 mg/kg ADX_5322_A02 anti-PD-L1 adnectin reduced tumor uptake at 2 h after injection by approximately 70%, whereas HT-29 uptake remained unchanged, demonstrating PD-L1-specific binding. Biodistribution in a nonhuman primate showed binding in the PD-L1-rich spleen, with rapid blood clearance through the kidneys and bladder. Binding in the PD-L1(+) spleen was reduced by coadministration of BMS-986192. Dosimetry estimates indicate that the kidney is the dose-limiting organ, with an estimated human absorbed dose of 2.20E-01 mSv/MBq. Conclusion:18F-BMS-986192 demonstrated the feasibility of noninvasively imaging the PD-L1 status of tumors by small-animal PET studies. Clinical studies with 18F-BMS-986192 are under way to measure PD-L1 expression in human tumors.

Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging.

UNLABELLED: Recent developments have established molecular imaging of mouse models with small-animal PET and bioluminescence imaging (BLI) as an important tool in cancer research. One of the disadvantages of these imaging modalities is the lack of anatomic information. We combined small-animal PET and BLI technology with small-animal CT to obtain fusion images with both molecular and anatomic information. METHODS: We used small-animal PET/CT and BLI to detect xenografts of different cell lines and metastases of a melanoma cell line (A375M-3F) that had been transduced with a lentiviral vector containing a trimodality imaging reporter gene encoding a fusion protein with Renilla luciferase, monomeric red fluorescent protein, and a mutant herpes simplex virus type 1 thymidine kinase. RESULTS: Validation studies in mouse xenograft models showed a good coregistration of images from both PET and CT. Melanoma metastases were detected by 18F-FDG PET, 9-[4-(18)F-fluoro-3-(hydroxymethyl)butyl]guanine (18F-FHBG) PET, CT, and BLI and confirmed by ex vivo assays of Renilla luciferase and mutant thymidine kinase expression. 18F-FHBG PET/CT allowed detection and localization of lesions that were not seen on CT because of poor contrast resolution and were not seen on 18F-FDG PET because of higher background uptake relative to 18F-FHBG. CONCLUSION: The combination of 18F-FHBG PET, small-animal CT, and BLI allows a sensitive and improved quantification of tumor burden in mice. This technique is potentially useful for the study of the biologic determinants of metastasis and for the evaluation of novel cancer treatments.

Monte carlo simulations of dose from microCT imaging procedures in a realistic mouse phantom.

The purpose of this work was to calculate radiation dose and its organ distribution in a realistic mouse phantom from micro-computed tomography (microCT) imaging protocols. CT dose was calculated using GATE and a voxelized, realistic phantom. The x-ray photon energy spectra used in simulations were precalculated with GATE and validated against previously published data. The number of photons required per simulated experiments was determined by direct exposure measurements. Simulated experiments were performed for three types of beams and two types of mouse beds. Dose-volume histograms and dose percentiles were calculated for each organ. For a typical microCT screening examination with a reconstruction voxel size of 200 microm, the average whole body dose varied from 80 mGy (at 80 kVp) to 160 mGy (at 50 kVp), showing a strong dependence on beam hardness. The average dose to the bone marrow is close to the soft tissue average. However, due to dose nonuniformity and higher radiation sensitivity, 5% of the marrow would receive an effective dose about four times higher than the average. If CT is performed longitudinally, a significant radiation dose can be given. The total absorbed radiation dose is a function of milliamperes-second, beam hardness, and desired image quality (resolution, noise and contrast). To reduce dose, it would be advisable to use the hardest beam possible while maintaining an acceptable contrast in the image.

A method of image registration for small animal, multi-modality imaging.

Many research institutions have a full suite of preclinical tomographic scanners to answer biomedical questions in vivo. Routine multi-modality imaging requires robust registration of images generated by various tomographs. We have implemented a hardware registration method for preclinical imaging that is similar to that used in the combined positron emission tomography (PET)/computed tomography (CT) scanners in the clinic. We designed an imaging chamber which can be rigidly and reproducibly mounted on separate microPET and microCT scanners. We have also designed a three-dimensional grid phantom with 1288 lines that is used to generate the spatial transformation matrix from software registration using a 15-parameter perspective model. The imaging chamber works in combination with the registration phantom synergistically to achieve the image registration goal. We verified that the average registration error between two imaging modalities is 0.335 mm using an in vivo mouse bone scan. This paper also estimates the impact of image misalignment on PET quantitation using attenuation corrections generated from misregistered images. Our technique is expected to produce PET quantitation errors of less than 5%. The methods presented are robust and appropriate for routine use in high throughput animal imaging facilities.

Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging.

UNLABELLED: The microPET Focus is the latest generation microPET system dedicated to high-resolution animal imaging and incorporates several changes to enhance its performance. This study evaluated the basic performance of the scanner and compared it with the Primate (P4) and Rodent (R4) models. METHODS: The system consists of 168 lutetium oxyorthosilicate (LSO) detectors arranged in 4 contiguous rings, with a 25.8-cm diameter and a 7.6-cm axial length. Each detector consists of a 12 x 12 LSO crystal array of 1.51 x 1.51 x 10.00 mm3 elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical fiber bundles. The system was evaluated for its energy and spatial resolutions, sensitivity, and noise equivalent counting rate. Phantoms and animals of varying sizes were scanned to evaluate its imaging capability. RESULTS: The energy resolution averages 18.5% for the entire system. Reconstructed image resolution is 1.3-mm full width at half maximum (FWHM) at the center of field of view (CFOV) and remains under 2 mm FWHM within the central 5-cm-diameter FOV in all 3 dimensions. The absolute sensitivity of the system is 3.4% at the CFOV for an energy window of 250-750 keV and a timing window of 10 ns. The noise equivalent counting-rate performance reaches 645 kcps for a mouse-size phantom using 250- to 750-keV and 6-ns settings. Emission images of a micro-Derenzo phantom demonstrate the improvement in image resolution compared with previous models. Animal studies exhibit the capability of the system in studying disease models using mouse, rat, and nonhuman primates. CONCLUSION: The Focus has significantly improved performance over the previous models in all areas evaluated. This system represents the state-of-the-art scintillator-based animal PET scanner currently available and is expected to advance the potential of small animal PET.

Attenuation correction for small animal PET tomographs.

Attenuation correction is one of the important corrections required for quantitative positron emission tomography (PET). This work will compare the quantitative accuracy of attenuation correction using a simple global scale factor with traditional transmission-based methods acquired either with a small animal PET or a small animal x-ray computed tomography (CT) scanner. Two phantoms (one mouse-sized and one rat-sized) and two animal subjects (one mouse and one rat) were scanned in CTI Concorde Microsystem's microPET Focus for emission and transmission data and in ImTek's MicroCAT II for transmission data. PET emission image values were calibrated against a scintillation well counter. Results indicate that the scale factor method of attenuation correction places the average measured activity concentration about the expected value, without correcting for the cupping artefact from attenuation. Noise analysis in the phantom studies with the PET-based method shows that noise in the transmission data increases the noise in the corrected emission data. The CT-based method was accurate and delivered low-noise images suitable for both PET data correction and PET tracer localization.

Perceptions of risk factors of cardiovascular disease and cardiac rehabilitation: a cross-sectional study targeting the Chinese population in the Midlands, UK.

OBJECTIVES: To find out and explore the knowledge and opinion of Chinese people on cardiovascular disease and awareness of cardiac rehabilitation. DESIGN: A cross-sectional study using 14-item bilingual (Chinese and English) questionnaires that include information on demographics, health status, cardiovascular disease related knowledge and perception, and awareness and understanding of the cardiac rehabilitation programme. SETTING: Chinese community groups in the Midlands, UK from January to April 2008. PARTICIPANTS: 436 questionnaires from Chinese adults over 18 were obtained. MAIN OUTCOME MEASURES: Current knowledge and attitude towards cardiovascular disease and awareness of cardiac rehabilitation. RESULTS: Obesity was the most common risk factor identified by 80.7% of participants. Those originated from China had significantly less knowledge compared with subjects from other countries (p<0.001). People who have had exposure or experience of cardiac disease rated a higher risk of cardiac disease for Chinese living in the UK than people without experience. A majority (81.7%) used orthodox medicine and perceived it to be most effective against cardiac disease. Only 30% of participants were aware of cardiac rehabilitation. CONCLUSION: The coronary artery disease (CAD) risk factors of Chinese population have increased significantly in the last decade. Cardiac rehabilitation awareness was poor among the sample population of this study and language barrier is still a problem. More large studies on Chinese population assessing CAD risk should be done to provide more evidence on CAD prevention for this growing population in the Western world.