Brain candy for the molecular age

Stealthy magnetophages and bacterial contrast agents were among the brain candies enjoyed last week by a community starved for something new. These treats were rich in potential, creamy smooth in creativity, and a welcome change from the meat and potatoes diet that has been fed to the MR community for the past 20 years.

What was state-of-the-art in MR contrast two decades ago is, sadly, still state-of-the-art today. Magnevist, the pioneering central nervous system agent that got the ball rolling, remains on top. The fact that sales of this and competing agents are prospering partly because of their use outside the CNS speaks volumes about the lack of technological innovation in this market segment.

Attempts to develop agents specific to the abdomen and vasculature have had limited success. It is little wonder then that discussions of future developments have lately centered around smart MR contrast agents, molecules whose magnetic properties change depending on the chemical environment surrounding them. Such agents might reflect changes in acidity or calcium concentration, which themselves are related to physiological changes such as enzymatic alterations caused by the activation of a gene. They promise to bring MR into the age of molecular imaging. And there seems no end to the creativity that might result from such exploration.

At the Miami meeting of the International Society for Magnetic Resonance in Medicine, dozens of papers addressed these possibilities. One posited genetically engineered Salmonella with a bent for cancer cells carrying gadolinium and anticancer drugs to tumors in the body. Another addressed magnetophages (paramagnetic molecules attached to viruses called bacteriophages) that seek out specific bacteria, providing a highly targeted molecular contrast agent for MR.

Such possibilities can recharge the batteries of invention worn down by decades of sameness. But they are, at least for the near term, little more than a sugary confection, satisfying in concept but lacking in practicality.

One need only look at the difficulties that have befallen hyperpolarized gases to realize that promise is not enough to hang MR hats on. Only five years ago, very smart people were predicting that hyperpolarized gases would generate tens of millions of dollars in annual sales, open the lungs to MR assessment, and vastly improve clinical outcomes for people with pulmonary disease. None of this happened, but not for lack of trying. A dedicated community of luminaries and a corporate champion, GE Healthcare, continue to press this technology, looking beyond noble gases to liquid formulations of carbon and nitrogen.

The tribulations of companies pursuing more mainstream ideas underscore the challenge of developing contrast agents. Epix Medical, with its blood pool agent AngioMark, and Advanced Magnetics, with its lymph node agent Combidex, each overcame technical challenges only to run aground at the FDA.

The problems facing MR contrast agents past, present, and future provide a sampling of what the imaging community has to overcome if it is to capitalize on the potential of molecular imaging. It must come up with ways to make these agents successful because they are the forerunners of a new age of medicine.