Biomedical Applications of Emission Tomography - Correction Techniques in Emission Tomography - page 23

new insight into the role of cardiac nerves in various cardiovascular disorders
(see above).
Apart from the presynaptic innervation, the postsynaptic density of
adrenoceptors to which catecholamines bind and whereby they mediate intra-
cellular responses is an important parameter. adrenoceptors have been quan-
tied by using radiolabeled adrenoceptors antagonists and PET. [ 11 C]CGP
12177 is a non-selective adrenoceptor antagonist that has seen the most
widespread application in clinical research [22, 14].
PET, with its capability to quantify transmitter synthesis and transport
as well as adrenoceptor density non-invasively in vivo, needs sophisticated
tracer-kinetic modelling. In the field of PET radiopharmaceuticals for assess-
ment of cardiac sympathetic nervous function, two tracer-specific models ex-
ist. Presynaptic norepinephrine re-uptake function is assessed by calculation of
the distribution volume (V d ) of 11 C-hydroxyephedrine using a single compart-
ment model and least square non-linear regression analysis to provide influx
and eux rate constants [22]. Delforge et al. [5] described a model for mea-
surement of myocardial adrenoceptor density (B max ) with a double injection
protocol of 11 C-CGP 12177, which implies two injections of different amounts
of radioactivity and a cold substance, using a graphical approach. The main
advantage of this approach is that the results are obtained without having to
measure the input function and without estimating the metabolites. With this
model and technique, the quantification of the active adrenoceptors located
on the surface of the plasma membrane can be achieved in vivo since 11 C-
CGP 12177 has hydrophilic characteristics and therefore does not cross the
cell membranes significantly. Modelling of tracer kinetics to quantify receptor
densities and nerve function is critically dependent on precise correction meth-
ods for emission tomography data taking into account attenuation, extravas-
cular volume fractions and such. Figure 2.5 demonstrates the quantification
of individual presynaptic and postsynaptic sympathetic innervation through
kinetic modelling of two dynamic PET studies in patients with different forms
of arrhythmias.

2.4.3.5 Multiparametric imaging of brain tumors

Gliomas are the most common primary brain tumors with an incidence
of 5-10/100.000. Gliomas still carry a very limited prognosis and together
with all intra-cranial neoplasms they are the second most common cause of
death from an intracranial disease after stroke. In recent years imaging based
on MRI and PET has considerably improved the management of patients
with gliomas. The most common PET markers implemented are [ 18 F]FDG
for glucose consumption and cellular density, [ 11 C]-methyl -methionine (MET)
for amino acid transporter activity and neovascularisation, and [ 18 F]-uoro-L-
thymidine (FLT) for cellular thymidine kinase activity and tumor cell prolif-
eration. All imaging markers aim toward the characterization of the biological
activity of the tumor (Figure 2.6; [6]). In the clinical application this is espe-