Iterative optimal design of PET experiments for estimating β-adrenergic receptor concentration

Abstract

To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S)-fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity.

Measurement of 5-HT1A Receptor Density and in-vivo Binding Parameters of [18F]mefway in the Nonhuman Primate

“…C pi represents the molar concentration of mefway in the plasma (pmol/mL) and serves as the input function. For studies with multiple injections, B and F compartments are created for each injection (i) (Delforge et al, 1990;Muzic et al, 2000;Christian et al, 2004;Morris et al, 2004), as described by the differential equations:…”

“…The M-I method provides a measure of receptor density that is independent of the characteristics of the radioligand, unlike the 'binding potential' metric obtained with tracer-only PET studies, which represent a composite function of B max and ligand-receptor affinity (Innis et al, 2007). The M-I methods have also been used for the measurement of B max in the peripheral benzodiazepine (Delforge et al, 1996), badrenergic (Muzic et al, 2000;Salinas et al, 2007), dopamine transporter (Morris et al, 1996;Poyot et al, 2001), dopamine D2 (Delforge et al, 1999;Christian et al, 2004;Mauger et al, 2005;Vandehey et al, 2010), and nicotinic acetylcholine (Gallezot et al, 2008) receptor systems.…”

Imaging Mouse Cancer Models In Vivo Using Reporter Transgenes

“…Thus the location of picomolar amounts of probe can be readily detected and accurately quantified irrespective of tissue depth (Muzic et al 2000;Madsen et al 2011). As the positron travels a short distance before annihilation, the resolution of this technique is 1 mm 3 and produces images showing areas of relative signal intensity as opposed to anatomic detail.…”

SPECT imaging of the α4β2 nicotinic receptor using [5‐123I]A85380

“…11 C]Nicotine 1 has been used in a number of PET imaging in humans, [6][7][8][9][10] however [ 11 C]nicotine demonstrates rapid dissociation from the receptor-ligand complex, high levels of non-specific binding, and strong dependency of accumulation on cerebral blood flow.…”