Cherry's miniature imagers cast giant shadow on scanner design

When Simon Cherry, Ph.D., began working on PET as a postdoctoral fellow at the University of California, Los Angeles, he recognized the gap between identifying molecular drug targets and providing real-world clinical applications.

"I realized that imaging could play a bridging role," he said.

Since then, he's been building bridges between academic and preclinical research as a professor of biomedical engineering and director of the Center for Molecular and Genomic Imaging (CMGI) at the University of California, Davis.

Cherry made his mark in the PET world at UCLA in the late 1990s, when he developed the first microPET scanner in the laboratory of Edward Hoffman, Ph.D. The invention addressed the need for images of small animals used to model human disease, since human-scale PET scanners already available did not offer the resolution necessary for these studies. The miniaturized version of PET designed for preclinical studies of mice opened the door to new research realms.

"We've enabled biologists to use this technology," Cherry said. "That's our legacy."

About 120 microPET scanners derived from the original invention have been sold throughout the world, and hundreds of research papers have been based on their use. MicroPET research spans many fields: neurology, oncology, immunology, and others.

"One of the real lessons we're learning is that even in genetically identical mice there are differences in responses to therapies," Cherry said.

In conventional preclinical trials, results were pooled, washing out individual variability.

"Imaging keeps us more informed all the way along the drug discovery continuum," he said.

Alone, PET cannot provide detailed anatomic information, so Cherry added CT to his design in the early 2000s. With the addition of CT, the PET signal can be pinpointed to a precise anatomic location, particularly in bone and lungs.

Cherry is also working on a "much richer combination than microPET/CT" by marrying microPET with MRI. MRI yields detailed anatomic information, just as CT does. But it offers additional advantages. MRI does not require a second dose of radiation. Extra radiation can interfere with a study, particularly if the immune system is under investigation and unintentionally stimulated by the radiation. MRI also distinguishes differences in soft tissue, such as gray and white brain matter, much better than CT. With microPET/MRI, researchers could investigate new avenues, such as temporal imaging using two molecular imaging agents simultaneously.

Incorporating MRI has been challenging. The PET detector could not simply be placed inside the MR machine because the magnets would interfere with the photomultiplier tube that converts the radioactive PET signal into electricity. Using fiber-optic cables to move the signal and photomultiplier outside the magnets was possible, and Cherry demonstrated the feasibility of this option in the late 1990s. But the result was an ungainly tangle of wires not ideal for commercial development. Only recently, has a technological breakthrough-the invention of a positron-sensitive avalanche photodiode to replace the traditional photomultiplier-allowed microPET/MRI to advance. Still, the machine is in very early stages of development, according to Cherry.

"I'd like to increase the use of PET in biological research," he said.

He's pursuing that goal both in his own lab and as director of CMGI. To that end, the 4000-square-foot CMGI has imaging facilities exclusively for animals: microPET, microCT, microPET/CT, optical imaging, ultrasound, and, eventually, MRI.

In his lab, Cherry balances high-risk research projects with applied work, such as developing a low-cost microPET machine designed for the lab bench. He's also collaborating with another lab to develop a breast cancer PET scanner with high resolution, designed for cases in which traditional mammography is inadequate.

For now, though, Cherry is taking a sabbatical from his imaging work to delve into molecular biology under the direction of Dr. Hsing-Jien Kung at the UC Davis Cancer Center. Cherry isn't sure exactly where his newfound knowledge will take him. But it will no doubt allow him to better understand the needs of principal investigators using his technologies.