Challenging Nuclear Cardiology Research: Stimulating Discovery, Validation, and Clinical Relevance

Abstract

Most of what we know of nuclear cardiology has been discovered in the last nearly 50 y. In tracing the history of nuclear cardiology research, we find that, early on, it attracted the attention of some of the best minds in nuclear medicine and cardiology, who were working closely with highly talented, skilled, and academically engaged radiochemists, physicists, and technologists. This successful blueprint of an integrated approach to scientific discovery that addresses clinically relevant issues remains true today and should remain true in the future.Nuclear imaging expands the traditional imaging of anatomic structures to physiologic and biochemical structures or biologic processes. A key attribute of nuclear molecular imaging is that it allows clinicians to visualize cellular functions that influence progression of disease, therapeutic responsiveness, and ultimately patient outcome. Such molecularly targeted imaging has the potential to direct new drug development and new gene-and cellbased therapies and to determine the subset of patients who are most likely to respond to such therapies. Since the introduction of myocardial perfusion (1) and metabolic agents (2), there has been explosive growth in the literature on, and National Institutes of Health funding of, experimental studies on cardiovascular molecular imaging. Unfortunately, such advances in the basic sciences have not translated into clinically approved diagnostic or therapeutic agents. Important challenges that have limited the progression to clinical reality include cost, scalability, and regulatory burden (3). HOW TO INCREASE THE RELEVANCE OF RESEARCHFor a productive pursuit of scientific investigation, it is essential that a lead or idea be clinically relevant and that it address an unmet need. Next, there must be methodologic and imaging procedures capable of visually or quantitatively capturing the specific biologic process of interest, such as metabolic pathway, receptor biology, or enzyme regulation. For example, the ability to image the metabolic shift of energy production from fatty acids to glucose in the setting of reduced myocardial blood flow at rest has helped explain the pathophysiology of viable, hibernating myocardium and critical patient management decisions regarding coronary artery revascularization, left ventricular assist device placement, cardiac transplantation, or continued medical therapy (4,5).In medicine, we must try to infer the nature of the biologic system from measured dynamic function and to derive information about their causes and interrelations in order to understand normal and abnormal disease conditions. Dynamic and quantitative analysis is a key virtue of nuclear radiotracer-based imaging. It allows assessment of changes in enzymatic or receptor activity as a function of disease severity and time. Creation of the time profile of the change in disease process is critical in following progression or regression of disease and the therapeutic effect of medications over a long period, such as days, weeks, or months....

Comparison of Echocardiography and Myocardial Scintigraphy to Detect Cancer Therapy-Related Cardiovascular Toxicity in Breast Cancer Patients

“…It may take some time until the tracer 123 I-BMIPP is widely recognized, as it is not yet widely used in practice. For example, it has not yet been approved by the Food and Drug Administration (FDA) in the USA [ 25 ]. Tl/BMIPP myocardial scintigraphy is recommended in class IIb for diagnosis of vasospastic angina in Japanese guidelines, but it is not yet referred to in Western guidelines [ 26 , 27 ].…”

“…Tl/BMIPP myocardial scintigraphy is recommended in class IIb for diagnosis of vasospastic angina in Japanese guidelines, but it is not yet referred to in Western guidelines [ 26 , 27 ]. However, 123 I-BMIPP has been introduced as a promising new tracer in reviews internationally [ 4 , 10 , 25 ]. 123 I-BMIPP scintigraphy (or Tl/BMIPP dual-isotope myocardial scintigraphy) may have other roles than echocardiography in evaluating CVR-CVT.…”

Iodine-123 β-methyl-P-iodophenyl-pentadecanoic Acid (123I-BMIPP) Myocardial Scintigraphy for Breast Cancer Patients and Possible Early Signs of Cancer-Therapeutics-Related Cardiac Dysfunction (CTRCD)

“…123 I-BMIPP was introduced as a promising new tracer in some reviews [5,6,14]. 123 I-BMIPP has been used in Japan for over 2 decades, although it has not yet been approved by Food and Drug Administration (FDA) in the U.S. [14]. There are only a few reports regarding 123 I-BMIPP scintigraphy performed for CTRCD [7,15,16].…”