Introduction

The discovery and development of novel treatments is a lengthy and costly endeavor: for drug candidates entering clinical trials between 1989 and 2002, the estimated cost per new drug varied from approximately 500 million to more than 2 billion U.S. dollars. Biomarkers – objective and measurable responses to a putative drug candidate – have been heralded as one potential solution to the ever-increasing expenditure of developing new medicines, and anatomical or functional medical imaging can be one tool in the armamentarium of biomarkers. Conceptually, the utility of imaging biomarkers for facilitating drug development, especially go/no go decisions in early development, includes the following:

• confirming the presence of a drug target in a (sub)population entering a clinical trial (e.g., accumulation of β-amyloid, as measured with positron emission tomography [PET] and a specific ligand for β-amyloid in the brain of patients entering a clinical trial for a novel Alzheimer's drug candidate);

• assessing target engagement of a novel drug candidate (e.g., confirmation of dopamine-2 [D2]) receptor antagonism of antipsychotics using PET imaging of [C]-raclopride displacement);

• demonstrating a functional effect of a drug on a mechanism- or disease-relevant biological parameter (e.g., blockade of ketamine-induced functional magnetic resonance imaging [fMRI] signal in the central nervous system [CNS] by antipsychotics or glutamate-normalizing compounds);

• […]