NHLBI Working Group
Translation of Cardiovascular Molecular Imaging

Executive Summary

The National Heart, Lung, and Blood Institute convened a Working Group (WG) meeting on September 16-17, 2009, in Bethesda, Maryland to advise NHLBI on the future of translational cardiovascular molecular imaging (CVMI).The WG members included cardiologists, radiologists, imaging scientists, engineers, and basic scientists with an interest in CVMI. The goal of the meeting was to develop recommendations on how NHLBI could promote the translation of CVMI from the research laboratory into clinically-relevant areas such as diagnostics, monitoring of treatment efficacy, and drug development.

Discussion:

The WG first addressed the current state of the art of CVMI, reviewing each of the molecular imaging modalities in current use and assessing their complementary strengths and potential uses.  The WG then reviewed the current state of imaging for a broad range of cardiovascular applications, with a focus on areas where CVMI could fill unmet clinical needs in diagnosis and monitoring of cardiovascular disease. Disease areas covered included:

• Atherosclerotic plaque and transplant rejection
• Peripheral and carotid artery disease
• Heart failure
• Valvular disease
• Aortic aneurysms

The WG went on to identify areas where CVMI was likely to have an impact. There was consensus that development of molecular imaging probes should be driven by biological questions, placing an emphasis on novel targets with the ultimate goal of translation to clinical applications. Areas identified included:

• Enabling drug development through the development of agents, techniques, and valid small and large animal models to measure therapy responses non-invasively
• Improving our understanding of basic biologic processes
• Leveraging molecular imaging development and allied targeting strategies for delivery of novel therapeutics, including drugs, genes, and cells

Next the WG focused on the barriers to translation of CVMI. The costs associated with the movement of imaging probes to large animal models and ultimately with obtaining FDA approval for use in humans were identified as a major barrier. The WG felt strongly that the FDA needed to be involved as a partner in the development and evaluation of new agents and technologies, as well as in their approval and regulation. Leveraging existing facilities and programs at other institutes was viewed as a potential way of developing synergies and reducing costs. Outreach to professional cardiovascular societies such as AHA and ACC through activities such as CVMI symposia at the annual meetings of these societies would provide a mechanism to increase awareness of the potential of CVMI in the cardiovascular community.
Finally, the WG developed a series of prioritized recommendations on how NHLBI should promote the translation of CVMI:

• Create a mechanism to facilitate faster and more cost effective translation from small animals to large animals and humans, with support for development of GMP facilities, GMP-grade products, and toxicology testing
• Develop molecular imaging networks or centers that; combine sites with expertise in different aspects of translation, e.g. small animal, large animal, and phase 1/2 clinical trials; foster industry collaborations; and promote interdisciplinary training
• Develop mechanisms, including new animal models, to validate novel emerging targets before imaging agent development
• Stimulate molecular imaging sub-studies in new NHLBI-sponsored clinical trials in areas such as peripheral arterial disease, stem cell therapies, heart failure, arrhythmias, and acute coronary syndromes

Publication Plans:

The WG will develop a report of the meeting for publication in an appropriate professional cardiovascular journal.

NHLBI Contacts:

Denis Buxton, PhD, NHLBI, NIH
buxtond@nhlbi.nih.gov

Simhan Danthi, PhD, NHLBI, NIH
ndanthi@nhlbi.nih.gov

Melissa Antman, PhD, NHLBI, NIH
antmanm@nhlbi.nih.gov

Working Group Members:

Co-Chairs:
Robert O. Bonow, MD, Northwestern University, Chicago, IL
Ralph Weissleder, MD, PhD, Massachusetts General Hospital, Boston, MA

Members:
Vasken Dilsizian, MD, University of Maryland Medical Center, Baltimore, MD
Zahi A. Fayad, PhD, Mount Sinai School of Medicine, New York, NY
Mario J. Garcia, MD, Mount Sinai School of Medicine, New York, NY
Michael R. Jaff, DO, Harvard Medical School, Boston, MA
Michael Klimas, PhD, Merck & Co., West Point, PA
Peter Libby, MD, Brigham and Women’s Hospital, Boston, MA
Matthias Nahrendorf, MD, PhD, Massachusetts General Hospital, Boston, MA
Albert J. Sinusas, MD, Yale University School of Medicine, New Haven, CT
Samuel A. Wickline, MD, Washington University, St. Louis, MO
Joseph C. Wu, MD, PhD, Stanford University School of Medicine, Stanford, CA

Last updated: December 4, 2009