Utility of positron emission tomography for drug development for heart failure

2016 ◽  
Vol 175 ◽  
pp. 142-152 ◽  
Author(s):  
Lampros Papadimitriou ◽  
Peter M. Smith-Jones ◽  
Chaudhry M.S. Sarwar ◽  
Catherine N. Marti ◽  
Kavitha Yaddanapudi ◽  
...  
2011 ◽  
Vol 1 (2) ◽  
pp. 137-151
Author(s):  
Ryogo Minamimoto ◽  
Chumpol Theeraladanon ◽  
Akiko Suzuki ◽  
Tomio Inoue

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Attila Feher ◽  
Nabil E. Boutagy ◽  
Evangelos K. Oikonomou ◽  
Yi-Hwa Liu ◽  
Edward J. Miller ◽  
...  

Background: Coronary microvascular dysfunction has been described in patients with autoimmune rheumatic disease (ARD). However, it is unknown whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) can predict adverse events in this population. Methods: Patients with ARD without coronary artery disease who underwent dynamic rest-stress 82 Rubidium PET were retrospectively studied and compared with patients without ARD matched for age, sex, and comorbidities. The association between MFR and a composite end point of mortality or myocardial infarction or heart failure admission was evaluated with time to event and Cox-regression analyses. Results: In 101 patients with ARD (88% female, age: 62±10 years), when compared with matched patients without ARD (n=101), global MFR was significantly reduced (median: 1.68 [interquartile range: 1.34–2.05] versus 1.86 [interquartile range: 1.58–2.28]) and reduced MFR (<1.5) was more frequent (40% versus 22%). MFR did not differ among subtypes of ARDs. In survival analysis, patients with ARD and low MFR (MFR<1.5) had decreased event-free survival for the combined end point, when compared with patients with and without ARD and normal MFR (MFR>1.5) and when compared with patients without ARD and low MFR, after adjustment for the nonlaboratory-based Framingham risk score, rest left ventricular ejection fraction, severe coronary calcification, and the presence of medium/large perfusion defects. In Cox-regression analysis, ARD diagnosis and reduced MFR were both independent predictors of adverse events along with congestive heart failure diagnosis and presence of medium/large stress perfusion defects on PET. Further analysis with inclusion of an interaction term between ARD and impaired MFR revealed no significant interaction effects between ARD and impaired MFR. Conclusions: In our retrospective cohort analysis, patients with ARD had significantly reduced PET MFR compared with age-, sex-, and comorbidity-matched patients without ARD. Reduced PET MFR and ARD diagnosis were both independent predictors of adverse outcomes.


2015 ◽  
Vol 33 (13) ◽  
pp. 1491-1504 ◽  
Author(s):  
Laetitia E. Lamberts ◽  
Simon P. Williams ◽  
Anton G.T. Terwisscha van Scheltinga ◽  
Marjolijn N. Lub-de Hooge ◽  
Carolien P. Schröder ◽  
...  

More than 50 monoclonal antibodies (mAbs), including several antibody–drug conjugates, are in advanced clinical development, forming an important part of the many molecularly targeted anticancer therapeutics currently in development. Drug development is a relatively slow and expensive process, limiting the number of drugs that can be brought into late-stage trials. Development decisions could benefit from quantitative biomarkers, enabling visualization of the tissue distribution of (potentially modified) therapeutic mAbs to confirm effective whole-body target expression, engagement, and modulation and to evaluate heterogeneity across lesions and patients. Such biomarkers may be realized with positron emission tomography imaging of radioactively labeled antibodies, a process called immunoPET. This approach could potentially increase the power and value of early trials by improving patient selection, optimizing dose and schedule, and rationalizing observed drug responses. In this review, we summarize the available literature and the status of clinical trials regarding the potential of immunoPET during early anticancer drug development.


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