Unidirectional Influx and Net Accumulation of PIB

Abstract

The compound {N-methyl-[(11)C]}2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, "PIB", measured by positron emission tomography, has been demonstrated to image brain beta-amyloid deposition in Alzheimer's disease (AD). In the present study the benefit of measuring the PIB accumulation rate together with the unidirectional influx of PIB into the brain was investigated in healthy control subjects and patients with AD. In a monkey changes in the influx rate constant K(1) of PIB closely followed changes in CBF, caused by alteration of Pa(CO2). In addition, K(1) was high both in the monkey and in humans, suggesting that this parameter reflects CBF. Most AD patients studied showed clearly higher accumulation rate for PIB than the controls in cortical brain areas, while a few patients showed as low accumulation as the controls. K(1) did not correlate with the accumulation rate, indicating that K(1) for PIB provides extra information besides the accumulation rate.

Keywords: Alzheimer´s disease; PET.; beta amyloid; cerebral blood flow; kinetic modeling.

Fig. (1)

The late uptake ratio in the frontal cortex for the HC group (n = 8) together with the single HC-Hi subject (the entry with the highest value) and all AD patients (n = 21). Data in the time interval 40–60 min were used.

Fig. (2)

Gjedde–Patlak plots for frontal cortex in (a) one subject in the HC group and (b) one patient in the AD-Hi group. The straight lines were fitted to the data in the time interval 30–60 min.

Fig. (3)

The result of applying the irreversible two-compartment model (three rate constants, input-3k model) to frontal cortex in one HC subject and one patient in the AD-Hi.

Fig. (4)

Parametric maps for PIB. Data from the same two experiments as in Fig. (2) were used. The maps show K_acc (left column) and K₁, (right column) for one HC (upper row) and one AD-Hi subject (lower row). For K_acc the colour scale goes from 0.01 to 0.055 min^-1, and for K₁ the scale goes from 0.0 to 0.5 min^-1.

Fig. (5)

Parametric maps from one brain slice in the monkey experiment. The upper row shows maps from the baseline experiments (from the left: CBF, K₁, K_acc), and the lower row shows the corresponding maps after increased Pa_CO2. For CBF the colour scale goes from 0.02 to 0.7 ml g^-1 min^-1, for K₁ the scale goes from 0.04 to 0.7 min^-1, and for K_acc the scale goes from 0.01 to 0.07 min^-1.