Methods for Obtaining the Arterial Input Function (AIF)

The identification of the arterial input function (AIF) can be achieved in two ways:

• Direct measurement of the AIF.
• Indirect derivation from the whole blood curve measured with the twilite.

Direct measurement of the arterial plasma input function

This method requires taking actual blood samples at various time-points, which have to be centrifuged. Then the total activity in plasma is measured in a defined aliquot. In addition, the total plasma activity has to be separated into true tracer and metabolites. If the metabolites do not enter the target organ, the input function needed for compartmental modeling is the time-course of true tracer in plasma. This procedure is cumbersome. It can be used in human studies, where enough blood can be drawn for the analysis. However in small animals like rats and mice, one has to resort to an indirect method to derive the plasma input function, which is also more convenient.

Indirect derivation from the whole blood curve measured with the twilite

This method consists in several steps to be performed as follows:

1. The time course of the activity in whole blood (C_WB) and total plasma activity (C_TP) is measured in a series of animals, using actual blood samples. The time-course of the ratio (total plasma/whole blood) is then approximated by a mathematical function, often one or a sum of exponentials.

(1)

2. The time-course of the ratio true tracer (C_FP) to total plasma activity C_TP is determined by metabolite analysis and is fitted by a mathematical function, which is often another single exponential or sum of exponentials

(2)

3. Once f1(t) and f2(t) are established, the true tracer concentration in arterial plasma can be derived from the whole blood input function measured with the twilite

(3)

PMOD allows calculating C_FP from the whole blood input function according to equation (3).