We read the comments of Borghammer and colleagues concerning our article with interest and wish to respond to the issues they have raised.
Despite some unequivocal limitations, the [18F]fluorodopa influx constant, Ki, derived by the multiple time graphical analysis approach (Patlak plot) is the best-validated and most widely used parameter in [18F]fluorodopa positron emission tomographic imaging for Parkinson disease (PD),1 and there is evidence in the literature that Ki is also a reliable marker for striatal dopamine cell counts and levels.2 The Ki value expresses the global net clearance of [18F]fluorodopa from the circulatory system by exchange across the blood-brain barrier, degradation of the tracer to F-dopamine by the dopa decarboxylase (aromatic acid decarboxylase), and storage in striatal nerve terminals. The k3D constant proposed by Borghammer and colleagues is a much more complex parameter hypothetically representing the striatal aromatic acid decarboxylase activity. To our knowledge, the k3D constant has not yet been validated in people with PD to reflect the disease process in clinical or histopathological terms. It is unclear whether the simple algebraic transformation of our Ki data into k3D values is reliably representative for the complex physiochemical process of [18F]fluorodopa metabolism in the brain. Moreover, a compensatory aromatic acid decarboxylase activity up-regulation has been proposed in early-stage PD.3,4 Therefore, the k3D constant might show falsely high values in affected patients with the consequence that disease progression is underestimated and that a fast exponential loss of dopaminergic capacity within the first years of the disease is missed. We used a logarithmic model of [18F]fluorodopa uptake decrease over time because of a significant correlation of the putaminal Ki decline with symptom duration prior to study inclusion and with the baseline putaminal Ki values. These findings argue against the proposed linear relationship between k3D values and symptom duration in the Figure by Borghammer and colleagues.