The procedures used to make PET imaging agents are currently under review by the FDA, and the Institute for Medical Research of the North Shore-Long Island Jewish (LIJ) Health system is only the third body in the country to be cleared under new draft guidelines on Good Manufacturing Practice (GMP) for these drugs.
North Shore-LIJ's cyclotron/radiochemistry facility is also the only one approved to make fludeoxyglucose F 18 at the highest strength currently available. It is twice the strength of the second institution's drug, and five times the strength of the first, which is no longer on the market.
Because radiopharmaceuticals like fludeoxyglucose F 18 decay rapidly, they must be used right away. However, the necessity to produce them in a hospital setting and then use them immediately poses a potential manufacturing quality and safety issue. If fludeoxyglucose F 18 is contaminated by microorganisms, other chemicals, by-products or impurities, it may affect the quality of the PET scan result and also pose a danger to patients. Therefore, manufacturing radiopharmaceuticals in a controlled environment that operates under rigorous quality assurance standards is key to safe production.
Thomas Chaly, chief of the Institute's cyclotron/radiochemistry facility and the author of its New Drug Application to the FDA, said that official regulation is expected within the next few years. FDA approval to manufacture a radiopharmaceutical depends not only on the success of the actual application but a site visit and inspection by the FDA of the facilities, equipment and procedures used in the manufacture of the drug.
Fludeoxyglucose F 18 is the most widely used radiopharmaceutical in PET scanning. A radiopharmaceutical is a specially designed drug that consists of a molecular compound that is similar to one normally used by cells -- in this case, glucose -- but which is tagged with radioactive atoms. When the cell absorbs the radiopharmaceutical, gamma rays are released as the unstable radioactive atoms rearrange themselves into a stable configuration. Travelling at the speed of light, the gamma rays allow the PET camera to generate a picture of those cells and organs at work. The amount of radiation to which a person is exposed is minimal and compares to that of a basic X-ray or CT scan.
Radioactive fluorine atoms are produced by a cyclotron, like the state-of-the-art GE PETrace Cyclotron purchased by North Shore-LIJ last year and installed at its research institute at a total cost of $2.6 million.
Once the radioactive atoms are produced, a sophisticated radiochemistry instrument such as a fludeoxyglucose synthesizer incorporates the radioactive atoms into a chemical compound such as deoxyglucose and produces the drug. fludeoxyglucose F 18 is manufactured in a saline solution, stored in glass vials and injected intravenously just prior to the actual PET scanning procedure.
The speed of radioactive decay of fludeoxyglucose F 18, or its half-life, is just under two hours. This means that every two hours, half of its radiation-emitting ability is lost. Therefore, the drug must be used the same day it is manufactured, often within just hours of production -- creating a challenge for transporting the drug over any distance. The drug strength produced depends on the capacity of the cyclotron. The greater the strength that can be made, the more drug is available for PET imaging studies and the farther the distance it can travel and still be active.
North Shore-LIJ currently sells and distributes fludeoxyglucose F 18 to numerous hospitals and PET facilities in the New York metropolitan area at about 40 per cent of its capacity. The high strength permits distribution as far away as Washington DC.
Fludeoxyglucose F 18 is currently approved for use in the US in the diagnosis of cancer, epileptic seizures and heart viability to determine, after a heart attack, if the heart muscle would benefit from surgery.