Dirk Bender, May 2016
Traditional nuclear medicine and PET both use diagnostic radioactive pharmaceuticals called tracers. PET tracers are labelled with radioactive atoms which decay and positrons (the antiparticles of electrons) are emitted.
Isotopes (used atoms) have a typical short half-life. 2 minutes for 15O and almost 2 hours for 18F. This short half-life means that tracers must be produced on site.
Tracers labelled with short-lived isotopes are singly produced - one tracer per patient. Tracers with a longer half-life are produced for groups of patients.
The goal of the radiochemistry/radiopharmacy unit, is to produce the necessary tracers for clinical and pre-clinical procedures.
Once the radioactive isotopes are produced, using a cyclotron, they are bound to larger molecules, which eventually become the radioactive tracers.
Production laboratories are all classified as a clean room Class A.
After production, and before use, all products are tested in the quality control laboratory, to ensure the specified quality standards. If the tracers meet the quality control requirements, they are released and prepared for distribution.
The radiopharmacy units meets the requirements of the Danish Medicines Agency regarding aseptic production of radioactive pharmaceuticals, and follows the principles of the Good Manufacturing Practice (GMP).
Each year, the PET Centre’s radiopharmacy unit produces approximately 12,000 doses of more than 35 different tracers which are used for human body scans and each year around 2 – 3 new tracers are developed.
Production starts at 4 a.m. and more than 30 people, including 9 chemists, are involved in the manufacturing process.
The radioactive isotopes are produced with the help of 2 cyclotrons (GE PETtrace and IBA 18/18) all year round.
Ga-68 generators and an Rb-82 generators are also used.
Production takes place in 4 radiochemistry production laboratories. The laboratories have 16 hot cells which contain 7 synthesis units for F-18 chemistry, 4 units for C-11 chemistry, 1 unit for Ga-68 chemistry and separate modules for O-15
Quality control is maintained by 5 Radio-HPLCs, 1 Radio-LCMS, 1 Radio TLC and 2 GCs.
The tracers are used in clinical and research studies. Further 65 tracers can be produced at short notice for pre-clinical scans.
The radiopharmacy unit produces around 13,000 doses each year in 2 radiochemistry labs with the help of Tc-99 generators and pre-fabricated kits. In addition to the nuclear medicine standard products, the following are also produced: Y-90 Dotatoc, C-14 Palmitat, H-3 Glucose, Y-90 Sirtec and Lu-177 Lutathera.
Distribution of tracers for clinical use
In 2002, the Danish Medicines Agency granted a marketing authorization of the most widely-used tracer, fluorine-18 FDG. FDG is delivered to PET centres at Aalborg University Hospital, Odense University Hospital, Aarhus University Hospital, Skejby, Herning Regional Hospital and Vejle Regional Hospital.
The tracers NaF and FDOPA are distributed to other hospitals. FDOPA is sent by air taxi to the Norwegian Radium Hospital, Oslo.