Flumazenil, COLD Input Curve

The Multiinjection, COLD model is used in combination with the tissue model for multi-injection studies with ¹¹C-Flumazenil as described by Delforge et al. [1]. Please refer to the documentation of the implemented tissue model for a more detailed description.

It is assumed that the total plasma activity of the labeled tracer C_Plasma(t) is loaded from the menu as illustrated below.

Operational Model Curve

The plasma activity of unlabeled (cold) ligand is calculated by using the information of the labeled (hot) ligand, scaling it proportionally to the applied dose, and applying the same metabolite correction. The metabolite corrected plasma activity of the labeled compound C_P(t) is calculated by

The calculation of the plasma activity of the unlabeled ligand C^u_P(t) is also performed differently in two time segments:

1. Following the cold-only injection at T₂ the input curve of the first hot injection at T₁ is scaled according to the dose ration and shifted to start at T₂.
2. Following the injection at T₃ with hot and cold ligand the input curve of the hot ligand is scaled, and a contribution of the first cold injection added which is decreasing by the metabolite build-up.

Parameter Fitting

Note that although the corresponding parameters have a fit box, they should normally be used for entering pre-determined values of injection times and metabolite correction parameters. The default parameters of the for the bi-exponential metabolite correction (A1, T1, A2, B2) used in this model are from [1].

Reference

Delforge J, Pappata S, Millet P, Samson Y, Bendriem B, Jobert A, Crouzel C, Syrota A: Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol. J Cereb Blood Flow Metab 1995, 15(2):284-300. DOI