Cardiovascular molecular imaging has an established and growing role in elucidating the underlying pathophysiologic mechanisms responsible for diseases of the myocardium and vasculature using small animals. Insights gained from molecular imaging research can identify targets for new drug development. Another goal is the development of molecular imaging agents for novel diagnostic purposes that ultimately can translate to clinical applications. Thus, there is great interest in expansion of molecular imaging probes beyond small animals to large animals and eventually to humans. Yet important challenges limit this progression to clinical reality related to scalability, cost, and regulatory burden.
Development of a new diagnostic imaging agent will undergo the same degree of regulatory oversight by the FDA as the development of a new drug. Bringing a new probe to patients will require millions of dollars and multiple years spent in pre-clinical work and Phase I and II clinical trials to obtain FDA approval. The incremental costs and delays related to development of GMP facilities and GMP-grade products, and the associated toxicology testing, represent additional barriers to clinical application. Further impediments relate to determination of pharmacokinetics and dosimetry. These challenges may be insurmountable for academic laboratories in which funding depends on peer-reviewed extramural grant support, as existing grant mechanisms are unlikely to support sophisticated GMP facilities or toxicology testing, whether performed internally or contracted through a third party. This impasse might be overcome with novel academic-industry partnerships, but the industry partner in turn would need to be convinced that the potential market for either the diagnostic agent or the resulting new therapeutic agent is sufficient to justify the investment in time and resources. Such partnerships could be enhanced if the NHLBI stimulated the research agenda and if the FDA were involved as a partner in the development and evaluation of new agents and technologies, as well as in their approval and regulation. Innovative mechanisms would need to be created 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.
Another barrier to clinical application is the small numbers of centers with current expertise and requisite facilities to perform high quality molecular imaging work. There needs to be expansion beyond the luminary centers. Leveraging existing facilities and programs at other institutions has the potential to develop synergies and reduce costs. This effort could lead to development of molecular imaging networks, which could then have a self-sustaining effect on the field by creation of interdisciplinary training, conferences, and workshops. Such networks could also combine sites with expertise in different levels of the translational paradigm, from small animal to large animal to early phase clinical trials. An imaging network or consortium could also have a leveraging effect to enhance NHLBI-academic-industry relationships.
The NHLBI could also stimulate the field by encouraging molecular imaging sub-studies in new institute-sponsored clinical trials. Outreach and partnering with cardiovascular associations and professional societies to increase awareness, through journals, young investigator conferences, and national meetings, of the potential of molecular imaging to advance the diagnosis, risk assessment, and treatment of patients with cardiovascular disease is another mechanism by which NHLBI could spur the translation of the field toward clinical applications.