The use of the exploratory IND in the evaluation and development of 18F-PET radiopharmaceuticals for amyloid imaging in the brain: a review of one company's experience.

AIM AND METHODS: The regulatory mechanism of exploratory INDs established in 2006 by the US Food and Drug Administration (FDA) is useful for the evaluation of tracer dose radiopharmaceutical agents, and especially valuable for development of amyloid imaging agents because of the absence of appropriate animal models. The authors employed exploratory INDs to study four related novel 18F-labeled positron emission tomography (PET) amyloid imaging agents, 18F-AV-19, 18F-AV-45, 18F-AV-138 and 18F-AV-144. These exploratory INDs contained preclinical data on the mechanism of action, secondary pharmacology, biodistribution, pharmacokinetics and dosimetry and results from a single dose, extended acute toxicology study. Each compound was then tested in a human PET study in up to 15 healthy elderly controls (HC) and 15 patients with AD. Compared to HC, patients with AD showed accumulation of tracer in cortical areas expected to be high in amyloid deposition with all four tracer compounds, and no serious adverse events were observed for any of the tracers.
RESULTS: .18F-AV-45 showed the best imaging characteristics and was chosen for further development under a traditional IND.
CONCLUSIONS: In summary the exploratory IND pathway was very useful for comparing four related agents with respect to efficacy (amyloid plaque binding), kinetics and dosimetry.