NIH Roadmap strategy boosts MI

Among hundreds of deserving research efforts, molecular imaging has emerged as a focal point in the National Institutes of Health Roadmap for medical research in the 21st century. The field is in prime position for the allocation of an estimated $2.1 billion in federal support for Roadmap initiatives over the next five years.

"This represents a tremendous boost to the status of molecular imaging," said Dr. King Li, associate director of radiology and imaging services at the NIH clinical center and member of the working group that will implement the Roadmap's molecular imaging initiatives. "We will be partnering with high-profile groups, like the molecular library group. That is a huge development. We have always wanted to partner with molecular library researchers."

The NIH Roadmap took shape shortly after the appointment of Dr. Elias Zerhouni in May 2002 as the first radiologist to head the NIH. Zerhouni convened a series of meetings involving more than 300 nationally recognized leaders in medical research, representing academia, industry, government, and the public at large. The group was charged with developing a framework for strategic investments NIH should make to optimize the Institutes' entire research portfolio.

First announced in September 2003, the NIH Roadmap has three broadly defined themes: New Pathways to Discovery, Research Teams of the Future, and Reengineering of the Clinical Research Enterprise. The Roadmap currently encompasses 27 initiatives that will be overseen by nine implementation groups, including one devoted to molecular libraries and imaging.

"We received hundreds of ideas, and we had to prioritize them," said Dr. Belinda Seto, deputy director of the National Institute of Biomedical Imaging and Bioengineering. "We had to decide what was realistic to do, but also what we could not afford not to do."

Initiatives included in the NIH Roadmap had to be considered trans-NIH. That is, they had to be something that no single institute could do by itself, something that would require the various institutes to join forces and work together.

"An initiative had to be truly transforming in terms of its impact," Seto said. "Given the rapid pace of advancement in imaging research, a truly transforming initiative for NIH is to develop high-resolution probes, which are critical in the acceleration of biomedical research to the next level. It would be a rate-limiting step, a barrier. If we can overcome this barrier, the rate of acceleration will be limitless."

BOOST FROM GENOME PROJECT

Molecular imaging has gotten a huge boost from completion of the Human Genome Project (HGP). Decoding of the human genome has yielded a catalog of three billion genetic sequences, which constitute the building blocks for discoveries related to the genetic pathways and networks responsible for health and disease, said Dr. Francis Collins, director of the National Human Genome Research Institute.

Filling in for Zerhouni as the Pendergrass New Horizons lecturer at the RSNA meeting last December, Collins said the HGP effort contributed to the identification of tens of thousands of potential genetic pathways and molecular targets that provide opportunities for development of new therapies. As a result, development of a molecular library to catalog the existing and emerging information is a priority of the NIH Roadmap.

"By discovering all the genes and their products, it is possible to go wildly beyond the traditional set of 500 or so drug targets," Collins said. "We have more targets than ever, and they will just sit there unless academic investigators, and the private sector, are empowered to go after them."

Collins noted that large libraries of chemical compounds make it possible to consider a high-throughput screening facility. Taking an assay through such a screening process could produce a short list of agonists and antagonists for a target. By means of screening robotics, as many as a million compounds might be evaluated affordably and in a manageable period of time, producing "hits" in the molecular library.

"Many of us concluded that the time is right for the NIH to invest in making this kind of capability available to individual investigators," Collins said.

Long-term program goals include enabling preclinical disease detection for a wide range of medical disorders; creating personalized, targeted therapies based on molecular profiling of cell and tissue function; and delineating data on cell physiology and function to guide development of personalized treatment and computational modeling. Collins called the goals ambitious but attainable within the current medical research climate.

The first of the initiatives will be launched this year, backed by about $130 million in funding for the fiscal year. At a briefing for the National Press Club last fall, Zerhouni said total funding for the Roadmap initiatives is expected to reach $2.1 billion over five years. The funding includes $500,000 five-year Director's Innovation Awards for individual researchers who have demonstrated promise for making discoveries relevant to the NIH's molecular imaging goals.

DATABASE NETWORK

The Roadmap has three key subinitiatives involving molecular imaging. The first is to develop a database of all ongoing molecular imaging efforts, including imaging programs and development of molecular imaging probes.

"The idea is to build a network or database and link that database to all the other molecular imaging databases that currently exist, including libraries of therapeutic targets that have been discovered," Li said. "Right now, there is no good database to show us what everyone is doing."

The second subinitiative encourages development of high-sensitivity imaging probes. Li said the goal is to increase sensitivity by 1000-fold over the capabilities of existing probes. The third subinitiative, which is the largest and most heavily funded, supports the goal of building a center devoted to development of molecular imaging probes. The initiative will be linked directly to the molecular library initiative headed by Collins.

Between September and December 2003, the NIH issued the first three requests related to Roadmap initiatives: a request for applications for development of high-resolution probes for cellular imaging; a request for information about molecular libraries/high-throughput screening centers; and a request for proposals for molecular libraries/small molecule repositories.

"The order of the appearance of these requests does not reflect their priority, just how quickly the various working groups could get their proposals finished," Seto said.

The NIH Roadmap's focus on molecular imaging will be a real boon to the young field, according to Dr. Philip Alderson, director of the National Academy of Radiology Research and a professor of radiology at Columbia University. The funding will provide much-needed support for promising molecular imaging programs and also encourage more investigation in the field. By linking programs in molecular imaging, molecular probes, and molecular libraries, the Roadmap is bringing together the critical elements for development of new, more specific therapies for a wide range of medical maladies.

"Better chemistry, in particular the chemistry needed for creation of targeted molecular agents, will be the key to better molecular imaging in the future," Alderson said.