Molecular imaging steers specialty to personalized care

August 1, 2007

The growing field of molecular imaging is helping nuclear medicine physicians identify pathways into personalized patient care. This overall assessment informed Dr. Henry Wagner's 30th annual highlights lecture at the 2007 Society of Nuclear Medicine meeting held in June in Washington, DC. Neuroimaging seems set to become the next new thing.

The growing field of molecular imaging is helping nuclear medicine physicians identify pathways into personalized patient care. This overall assessment informed Dr. Henry Wagner's 30th annual highlights lecture at the 2007 Society of Nuclear Medicine meeting held in June in Washington, DC. Neuroimaging seems set to become the next new thing.

Nuclear medicine pioneer Wagner, a professor of medicine, radiology, and environmental health sciences at Johns Hopkins University, distilled strategically relevant trends from more than 2200 oral and poster presentations.

Topics included small-animal studies, pandemic disease, the economic and clinical value of molecular imaging, regulatory issues, and new probes. He also visited recent advances in fused and hybrid imaging techniques and proposed extending the knowledge gained in oncology and cardiology to other subspecialty areas with great potential.

The brain would be the next big opportunity, according to Wagner. Statistics show that one-third of all prescription medications in the U.S. are given to affect mental activity. Drugs such as Prozac generate billions of dollars in sales.

But treatment of behavioral and mental disorders continues to be more or less a trial-and-error effort, like trying to treat hypertension without gauging blood pressure, Wagner said.

"Examining brain chemistry is not in the future any more. We can actually measure brain chemistry now," he said.

One poster presentation from Brookhaven National Laboratory researchers received special attention. Using PET with carbon-11-labeled monoamine oxidase A inhibitor clorgyline, the investigators found an association between MAO-A brain activity and violent behavior. The study became the 2007 SNM Image of the Year.

"That's an example of relating behavior and brain chemistry. And aggressiveness is not the only trait. There are innumerable traits," Wagner said.

Clinicians rely almost entirely on neuropsychological assessment of patients suffering from emotional, cognitive, and behavioral disorders such as depression, Alzheimer's disease, and schizophrenia. Currently, several types of drugs are under development in academic medical centers and by pharmaceutical companies. Some of these drugs also have the potential to become diagnostic agents. If that happens, they could allow not only diagnosis, but also treatment planning and even monitoring of treatment effectiveness at the molecular level, Wagner said.

"In the past, we treated patients based on statistical criteria from the study of large numbers of other patients. But now we can tailor the treatment to the patient. And part of that tailoring, in the case of brain diseases, is based on measuring brain chemistry," he said.

UPCOMING CHALLENGES

Fueling the SNM's Bench to Bedside initiative to expeditiously translate molecular imaging research into clinical practice takes more than good science and funding. Academic and corporate efforts need to undergo a sometimes lengthy FDA regulatory process. No new PET tracers, for example, have been approved in more than a decade.

Several routes can be taken, according to Wagner. For one, he proposed new regulations to allow the FDA's Radioactive Drug Research Committee program to sanction clinical research. Currently, the RDRC allows basic research on radioactive drugs only for fact gathering, not for diagnostic or therapeutic use.

But molecular imaging tracers, by definition, have no pharmacologic effect. If the RDRC were to allow clinical research, investigators would need to pursue inventive strategies to gain drug approval. For an agent that measures dopamine receptors, for instance, researchers would need to avoid tying it to a disease, such as schizophrenia or depression. The standard for approval should be the evidence that the drug measures what it is supposed to measure and that it is safe. That would greatly simplify the regulation, Wagner said.

"As an analogy, a thermometer is not approved in the context of treating pneumonia. It's approved in the context of being able to measure the patient's body temperature accurately," he said.

Other avenues contemplated include research with nanoparticles or enhancement of the local production and distribution of radiotracers. But the main idea remains bringing to the table all players involved-federal and state regulatory bodies, academic centers, and industry-to reach consensus on how best to approve these drugs for clinical use as quickly as possible.

"By working together with the FDA, we can do a much better job in translating these tracers into medical practice," Wagner said.

Developing probes that answer specific questions is paramount to incorporating molecular imaging into a model of personalized medicine and individualized healthcare, SNM president Dr. Alexander McEwan told Diagnostic Imaging.

"We have to develop the necessary clinical trial methodology that will validate the role of that agent in that individualized plan. The next thing is to work with the FDA to change, broaden, or modify the regulatory paradigm to let us actually validate these probes. None of them are going to be huge markets. They all are going to be niche products," he said.

The economic factor also emerged during Wagner's highlights lecture. He listed several examples of studies that stand out for providing enhanced diagnostic information but add little in terms of economic value. Imagers need to look at knowledge as a unit of value just as they do with space, personnel, or equipment, and they have to record the economic impact of a particular study, he said. Wagner discussed several ways to assess the value of a procedure, taking into account the benefit to patients in terms of treatment effectiveness, length of recovery, and survival.

"Increasing knowledge by molecular imaging is expensive. But making correct decisions decreases the cost of care for each patient," Wagner said.

Cost-effectiveness is an issue, McEwan said. Physicians now need to add an economic analysis to the clinical efficacy of trials to show that stratifying patients makes economic sense. This will put healthcare dollars to their best use and will also mean that the right patients will get the right treatment at the right time.

"If you take a drug like gemcitabine, which is effective in only 20% to 30% of patients with pancreatic cancer, wouldn't it be good if we could use molecular imaging to show which 20% or 30% of patients are going to respond?" he said.

For example, the use of fluorine-18 fluorothymidine (F-18 FLT) PET to predict the survival of patients with malignant glioma was also presented at the meeting. Whereas MRI took months to show evidence of response to therapy, the signs appeared on FLT-PET after just one week.

PERSONALIZED TOOLS

To gain the edge in personalized care, molecular imaging physicians need to focus on the molecular manifestations of diseases rather than their causes, Wagner said. Finding and observing these manifestations and using one or more of these variables may prove useful in deciding the appropriate course of treatment and monitoring its effectiveness.

Nuclear medicine physicians need, among other things, another "blockbuster probe," he said.

FDG is a wonderful drug, but it doesn't fill the bill for some conditions. Several papers have shown that certain tumors, such as those in the prostate or the brain, cannot be properly diagnosed with FDG because of low or inconsistent uptake. More powerful tracers are needed to fill the gap.

"There's a big demand for more tracers in oncology, and we predict this will be the next Centers for Medicare and Medicare Services-approved study. Will it be F-18 fluorothymidine, F-18 tyrosine, or another F-18-labeled amino acid, or will it be one of the new single-photon agents?" he said.

In the meantime, a number of small-animal studies are looking into the development of these new radiotracers in several clinical applications. Wagner also noted the growth potential for PET and SPECT, considering the booming sales of CT and MRI equipment, which hybrid imaging advocates see as an opportunity. New fusion imaging techniques and more powerful hybrid imaging devices, such as an MR/PET scanner, described at the meeting, show promise. Finally, there's also opportunity for molecular imaging to address the growing concern with the impending world epidemics of diabetes and other conditions. These could be perfect targets for molecular imaging, Wagner said.

Mr. Abella is associate editor of Diagnostic Imaging.