Analysis of 6-[18F]fluorodopamine PET data

6-[18F]fluorodopamine (6-[18F]FDA) is an analogue of dopamine, one of the catecholamines, that can be used for imaging sympathetic nervous system function. When produced in high specific activity, also other tissues than heart, with lower density of sympathetic nerves, can be studied without mass effects (Eskola et al., 2012).

Noradrenaline transporters in sympathetic nerve terminals transport 6-[18F]FDA into the cells, where it is converted into 6-[18F]fluoronoradrenaline (6-[18F]fluoronorepinephrine), and stored in vesicles by the vesicular monoamine transporter (VMAT). These steps are rapid, and allow to detect the tissue regions with intact sympathetic system. When sympathetic system is stimulated, noradrenaline and 6-[18F]fluoronoradrenaline are released from the vesicles; the washout rate of activity from tissue is quantitatively related to the sympathetic activity. In 6-[18F]FDA studies of the heart the decline of activity has been shown to be biexponential. When function

is fitted to the descending part of the myocardial activity curve, the half-life (t1/2 = ln(2)/λ) of the early and late phase is ∼5-15 min and ∼80-150 min, respectively (Goldstein et al., 1993; Coates et al., 1996).

Goldstein et al. (2002) developed a multicompartmental model for describing the kinetics of 6-[18F]FDA in heart tissue, but the model is too complex to be used in data analysis.


Metabolites in plasma

6-[18F]FDA is rapidly metabolized, and the fraction of authentic tracer in plasma is small just a few minutes after administration. Metabolites include 6-[18F]fluorodihydroxyphenylacetic acid, 6-[18F]fluorohomovanillic acid, and 6-[18F]fluorodopamine sulphate, but not 6-[18F]fluoronoradrenaline or its metabolites (Goldstein et al., 1993). Metabolism rate could be reduced and direction of metabolism could be modified by selective deuterium substitution of the tracer molecule (Ding et al., 1995).

Plasma-to-blood ratio

After venous infusion of 6-[18F]FDA, plasma-to-blood ratio increases slowly until after about 30 min it reaches a steady level of ∼1.4-1.5. When 6-[18F]FDA is incubated in a blood sample at 37 °C, the plasma-to-blood ratio decreases rapidly to a level of about 0.3 (Goldstein et al., 1993 and 1997).


See also:



References:

Goldstein DS, Holmes C. Metabolic fate of the sympathoneural imaging agent 6-[18F]fluorodopamine in humans. Clin Exp Hypertens. 1997; 19(1-2): 155-161. doi: 10.3109/10641969709080812.

Goldstein DS, Katzper M, Linares O, Kopin IJ. Kinetic model for the fate of 6-[18F]fluorodopamine in the human heart: a novel means to examine cardiac sympathetic neuronal function. Naunyn Schmiedebergs Arch Pharmacol. 2002; 365(1): 38-49. doi: .



Tags: , ,


Created at: 2018-04-12
Updated at: 2018-07-19
Written by: Vesa Oikonen