Introduction
18F-fluorodopa (FD) is a widely used positron emission tomography (PET) marker to investigate the integrity of the dopaminergic system. The tissue and plasma input FD uptake rate constants (Kocc and Ki)1, 2, 3 are used as measures of dopamine (DA) synthesis and storage. Recently, the DA effective distribution volume (EDV) was introduced as a measure of DA turnover (TO) (EDV = 1/TO) 4 . A relatively large increase in DA TO and a smaller decrease in DA uptake rate constant have been suggested as compensatory mechanisms in early Parkinson's disease (PD)4, 5. Here we investigated the age dependence of Ki, Kocc and EDV for caudate and putamen in healthy population and speculated on its implications on disease progression.
Methods
Nine healthy volunteers (age 58.1 ± 11.8 yrs, range 43–76) underwent a 4hrs long FD scan. Four 61 mm2 circular regions of interest (ROIs) were placed on each striatum, and six 270 mm2 circular ROIs were placed on the occipital cortex on five planes containing the striatal image on each frame of the dynamic sequence. Arterial blood samples were taken to obtain the plasma radioactivity time course with a subset analyzed for metabolites. Ki, Kocc and EDV values were calculated for the caudate and putamen separately with the left and right side averaged.
Results
A significant negative correlation was found between putamen Ki and age (r2 = 0. 92, p < 10-4) and between putamen EDV and age (r2 = 0.48, p = 0.039). No significant age correlation was found for all other measures (caudate Ki: r2 = 0.31, p = 0.12, caudate EDV: r2= 0.12, p = 0.36, Kocc putamen: r2= 0.35, p = 0.09 and Kocc cau: r2= 0.02, p = 0.70).
Discussion and conclusion
Ki showed a robust age dependence in contrast to Kocc for the putamen, while no parameter showed age dependence for the caudate. The literature addressing Ki and Kocc age dependence in healthy humans has reported contradictory results (6, 7 and others). Our results agree with work done in non-human primates 8 and suggest that Ki and Kocc have different sensitivities to age related degeneration of the dopaminergic function. EDV also shows an age related decline, implying an increase in DA TO in normal aging. Our findings imply that older individuals might have only limited ability to compensate for PD induced DA deficiency by increasing TO in contrast to younger ones. Likewise, a lower DA synthesis and storage rate in older individuals might lessen the system ability to maintain adequate DA levels in early PD. This might (i) permit a longer preclinical period in younger PD patients and (ii) explain a greater propensity for younger patients to develop motor complications.1, 2.