Simplified, noninvasive PET measurement of blood-brain barrier permeability

Blood-brain barrier (BBB) permeability to [⁶⁸Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, K_i, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant K_b (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (V_p). In the four normal volunteers the A, was 3.0 ± 0.8 x 10^-4 ml g^-1 min^-1 (mean ± SD) and the V_p 0.034 ± 0.007 ml g^-1. A net increase in K_s up to a maximum of 121.0 x 10^-4 ml g^-1 min^-1 (correspondent value of K_b = 0.025 min^-1) as well as an increase of V_p was observed in malignant tumors. The input function was calculated using both the [“GaJEDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of and V_p from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes.