In vivo imaging of fluorine-18 labeled radiotracers with positron emission tomography (PET) provides a powerful technique to rapidly measure drug properties, thus providing a valuable tool for ethical drug development. In 2004 and 2006, US FDA identified medical imaging and imaging biomarkers as critical tools to aid progress in therapeutic drug development. Recognizing the unique properties of PET radiotracers, specific guidelines for PET radiopharmaceuticals were published as current good manufacturing practice for PET drug products in 21 CFR part 212. In 2006 US FDA introduced the exploratory IND mechanism to allow study of radiotracers with minimal toxicological data, further facilitating radiopharmaceutical development. Development of radiopharmaceuticals is similar to that of classical pharmaceuticals but major advantages of radiopharmaceuticals are a lower cost of development and the low mass dose of material delivered to the subject (nano- to micrograms), which results in lack of pharmacological effects and a lower risk of undesired side effects. When a compound is synthesized, in-vitro binding assays are performed to determine its affinity for the target chosen as well its affinity for competing targets. Labeling and in-vivo imaging allows rapid screening of potential candidates in animal models. After validation of the accuracy of in vivo imaging measures, the radiopharmaceutical may be used to study therapeutic drugs by studies such as receptor occupancy. The exploratory IND mechanism has allowed rapid evaluation of new chemical entities as radiotracers for measurement of drug properties in humans. Although the guideline relaxes requirements for preclinical safety data, the preparation and compounding of the radiotracers into radiopharmaceutical drug products still require adherence to standards of drug manufacture. The tension between the need for rapid efficient process and the requirement for thorough control of all phases of manufacture provides one of the challenges of PET radiotracer research

Radiochemistry research to radiopharmaceutical drug manufacture: Promises and pitfalls

248th National Meeting (2014)

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