New Trends in Radiopharmaceutical Synthesis Using Positron Emitters: Quality Control
The synthesis of bioactive compounds labeled with positron emitters began in the early sixties but did not become significant until the late sixties and early seventies. The number of publications began to rise rapidly after the success of 18F-fluorodeoxyglucose in 1976. The major focus has been the use of carbon-11 and fluorine-18 although widespread use of oxygen-15 gas and water is also noteworthy. Nitrogen-13 except for 13N-ammonia has not enjoyed the same intense study. Synthesis with positron emitters has matured considerably in the last ten years. The needed excitation functions measured in the range accessible by “medical” cyclotrons have all been published. Precursor synthesis has become routine although refinements of standard methods still appear. A similar situation applies to targetry for 11C, 13N, 15O and 18F. The ease of obtaining 11CO2 [and therefore 11CH3] and 18F has lead to a large increase in papers involving methylation of amino or phenol groups and the use of aliphatic and aromatic displacement reactions with fluoride ion and frequently (unfortunately) without substantial pharmacological or biomedical justification. Nevertheless, more complex and rapid syntheses are being reported as are new techniques for accelerating reactions such as microwaves and sonication. With the rapid growth of clinical PET, regulatory aspects become increasingly demanding and quality assurance must become an integral feature of any PET project. Automation of synthesis becomes mandatory for those products in daily use. Thus a discussion of new techniques, trends in synthesis, quality control and the purposes of automation, hereafter, will be presented. Supported by USDOE and OHER.