Short half-life handicaps clinical adoption of carbon-11 radioisotope

Time is not on the side of molecular imaging researchers who hope to expand the use of the carbon-11 tracer into clinical PET practice.

Carbon-11 is popular with MI scientists, but its short 20-minute half-life has raised formidable barriers for its adoption outside of academic healthcare. Most community-based hospitals cannot afford an onsite cyclotron that is essential for its production and swift delivery to radiology departments for diagnostic use. Due to their small numbers, C-11 advocates have been discouraged from seeking federal regulatory clearance and reimbursement. Their inability to take action has contributed to disincentives for clinical use of C-11.

The migration of molecular probes from bench to bedside would be swifter and cheaper if C-11 were as easily accessible as fluorine-18, which can be produced and distributed from regional radiopharmacies because of its six-hour half-life.

Basic scientists often use C-11 because the high-energy positron-emitting isotope is easily bonded to most chemical compounds that show diagnostic or therapeutic promise. It does not alter the structure, reaction time, or mechanisms of action used by biological agents, and it labels molecules without changing their biological specificity, maximizing the probability of successful migration from the laboratory to animal and human testing.

C-11's 20-minute half-life can be advantageous, said Dr. Juri Gelovani, director of experimental diagnostic imaging at M.D. Anderson Cancer Center in Houston. It minimizes radiation exposure and enables repeat measurements without interference from previous studies.

Most F-18-based radiopharmaceuticals were first paired with C-11 in the laboratory. F-18 thymidine, for example, evolved from studies of C-11 thymidine that demonstrated its ability to measure cell proliferation.

Other investigational agents include C-11 PIB for Alzheimer's disease, C-11 methionine for tumor recurrence, C-11 choline for prostate cancer, and C-11 raclopride for neurological disorders. Designing chemical compounds bonding the base molecule of these agents with F-18 can be difficult, expensive, and time-consuming.

Experimental applications of C-11 probes have begun in humans at academic institutions equipped with cyclotrons and could potentially migrate quickly to community-based hospitals that acquire a baby cyclotron or linear accelerator designed to make C-11 generation more affordable. Systems from AccSys Technology, GE Healthcare, and Siemens Medical Solutions cost about $2 million.

But potential purchasers are biding their time because of regulatory and reimbursement problems, according to Ward Digby, director of biomarker product management at Siemens.

"It's a Catch-22, because since these carbon-based radioisotopes are not approved or reimbursable, they are not being used in local hospitals," he said. "Thus, community hospitals have no incentive to invest in a baby cyclotron. There is little interest, therefore, in conducting large, expensive clinical studies to get C-11 tracers approved."