Ra. Koeppe et al., [C-11] TROPANYL BENZILATE BINDING TO MUSCARINIC CHOLINERGIC RECEPTORS- METHODOLOGY AND KINETIC MODELING ALTERNATIVES, Journal of cerebral blood flow and metabolism, 14(1), 1994, pp. 85-99
Quantitative estimation of cerebral muscarinic receptors was investiga
ted with the use of the antagonist [C-11]tropanyl benzilate ([C-11]TRB
) and positron emission tomography (PET). Kinetic modeling alternative
s were examined with the goal of identifying an analysis method provid
ing stable receptor measures, yet avoiding biases from inappropriate r
eductions in model complexity. Dynamic PET scans were performed on six
young normal volunteers. Several modeling approaches yielding relativ
e receptor density measures were evaluated: (a) a single ''late'' scan
using relative tracer concentration values; (b) a slope estimate from
graphic analysis (Patlak plot); (c) a two-compartment, two-parameter
model (transport and total ligand distribution volume); (d) a three-co
mpartment, two-parameter model using the free + nonspecific distributi
on volume, DV', fixed to the cerebellar value; (e) an early scan for t
ransport, a fixed value for DV', and a single late scan for the bindin
g rate constant; and (f) a three-compartment, three-parameter model. B
oth computer simulations and PET scan results indicate all methods pro
vide receptor density index measures with the same rank order as in vi
tro measures. Oversimplified approaches (methods 1 and 2) yield a more
highly nonlinear relation between the estimated receptor density inde
x and the known receptor density than do methods retaining greater mod
el complexity (methods 3-6). However, noise propagation into the recep
tor measure is greater for the more complex methods. Reliable receptor
density information can be obtained from kinetic [C-11]TRB PET studie
s, with methods 3-5 providing the most appropriate levels of model com
plexity for estimates of relative muscarinic receptor density.