Molecular probe manufacturing process requires accurate, reliable liquid cooling.

A PET scan is a medical diagnostic test used to assess the chemical and physiological changes associated with disease.

Molecular probes are used in conjunction with positron emission tomography (PET) imaging. Given the highly sensitive nature of these products, it is not surprising that the process for manufacturing molecular probes requires accuracy and reliability throughout each stage, including cooling.

Recently, a liquid cooling solution was specified to support the molecular probe manufacturing process at key locations throughout the United States for PETNET Pharmaceuticals Inc., a Knoxville, Tenn.-based molecular imaging company that creates, manufactures and distributes molecular probes. PETNET also owns and operates the PETNET Positron Radiopharmacy Network of 35 manufacturing and distribution centers. A PET scan is a medical diagnostic test used to assess the chemical and physiological changes associated with disease. This, in turn, helps physicians manage their patients in the areas of oncology, neurology and cardiology. With PET, physicians can accurately identify and locate the extent of cancer and other disorders and avoid unnecessary surgery or inappropriate treatments.

The manufacturing of molecular probes used in PET requires the attachment of submass amounts of radioactive isotopes. The isotopes have a very short half-life; therefore, they must be made relatively close to the location of the actual PET scanner, necessitating installations throughout the United States. A cyclotron, or particle accelerator, is used to make the isotopes. The cyclotron requires chilled water to remove the heat it produces, and the amount of heat produced varies greatly depending on the cyclotron’s operating status. For example, in the idle or nonproduction hours of operation, the cyclotron produces approximately 1 ton of heat. During actual manufacturing periods, the cyclotron produces about 5 tons of heat. The change from requiring a small amount of cooling to requiring 5 tons of cooling is very quick.

To ensure reliable and consistent production, systems that chill water for isotope production require redundancy (on both system and component levels) and ruggedness for continuous operation. Also, they must be capable of handling wide temperature variations caused by the manufacturing process and seasonal temperature changes. Above all, there is little margin for error.

To ensure reliable and consistent production of the molecular probes that produce PET scans, the chiller must be capable of handling the wide temperature variations caused by the manufacturing process and seasonal temperature changes.

The Challenge

P.E.T. Net’s manufacturing process necessitated the use of auxiliary equipment to keep water circulating around the isotope at a constant chilled temperature of 45oF (7oC). To meet this challenge, PETNET contacted Gwyn Sales Inc., the Knoxville, Tenn., representative of Liebert Corp., a Columbus, Ohio-based manufacturer of environmental control systems. Mark Gwyn of Gwyn Sales Inc. recalls, “The initial challenge with PETNET was getting a handle on their requirements. They’re in the isotope manufacturing business, and they have to cool a machine that has varying requirements depending on what they’re doing at any particular time. When they’re attaching the isotopes, they need about 60,000 BTU/hr, which necessitates about 5 tons. Otherwise, they only need about 1 ton of cooling. Either way, they want 45oF water, and they don’t care how we get it to them. So we had to find the engineering data to determine how small the load is in the middle of the night vs. how large it is when they’re making product.”

Due to the cost of the cyclotron itself, the nature of the material it is manufacturing, and the requirements for precisely chilled water at all times, the cost of downtime is extreme. PETNET’s senior project manager Richard Dill says that as much as $10,000 a day could be lost at any given installation if isotope production was stopped.

For a process with strict temperature tolerances such as PETNET’s, connecting a critical application into a facility’s building chiller unit was not a workable solution. Water-cooled equipment relies on a continuous supply of liquid coolant to maintain processor temperature within tight tolerances. Conditions exceeding the temperature specifications or an interruption of coolant flow can cause sudden shutdown, interruption of operations and serious hardware damage. Moreover, building chillers recirculate water through pipes and components that do not meet the cleanliness requirements of medical equipment, and piping length and fittings can introduce transport lag, making temperature variation a near inevitability.

PETNET saw close coupling of the chiller and cyclotron as a way to solve this problem. By locating the chiller in close proximity to the equipment, long piping runs are eliminated and more precise control of the coolant temperature is maintained. As PETNET’s Dill says, “It is very difficult to make the product. The whole process to make a batch takes 5 to 6 hours. Two hours of that is to be supported by Liebert equipment. We start at midnight, and if we have a heat gap, then we need someone who can come in at odd hours and fix it. If you cannot consistently deliver the product, then your customer will go somewhere else.”

The right solution included key design features such as a semihermetic compressor, component redundancy and precise control of flow and temperature. In addition, PETNET sought a supplier whose equipment had a solid history of reliability where the chiller can run yearround down to -30oF (-34oC) outdoor ambient temperature. PETNET also required equipment with the ability to handle wide temperature variations caused by the manufacturing process and seasonal temperature changes. Finally, year-round service and support were important.

Selecting the Cooling System

Gwyn specified a chiller that is designed to provide fail-safe, 100 percent redundancy at the component and system levels with automatic switchover between two chillers in the event of any failure. Consequently, no single component failure will interrupt operation. With an operating temperature range of -35 to 100oF (-37 to 38oC), the chiller can operate in winter and summer conditions. And, with the addition of a 75-gal thermal storage tank built into the chiller housing, the unit always has the required chilled water available, no matter what state of operation the chiller is in.

The Liebert chiller model utilized at PETNET facilities contains multiple, totally independent cooling units for system redundancy. Its semihermetic compressor is designed to be more efficient than conventional hermetic compressors, and its historic service life is more than four times as long as its hermetic counterparts while providing a high energy-efficiency ratio. It provides a clean supply of water that will not disrupt sensitive equipment and prevents contamination from outside elements.

Proof of the chillers' suitability is in their performance since installation. According to Dill, PETNET has successfully run its manufacturing operations with no interruption after initial startup adjustments were made to modify each chiller relative to its particular site.

This article was contributed by Liebert Corp., part of Emerson Network Power, a manufacturer of precision cooling, HVAC and environmental control technologies. For more information, visit