[High non-specific binding of the beta(1) -selective radioligand 2-(125)I-ICI-H].
OBJECTIVE
As results of cardiac biopsies suggest, myocardial beta(1) -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac beta(2)-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess beta-adrenoceptors non-invasively. Among the novel racemic analogues of the established beta(1)-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to beta(1)-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective beta(1)-adrenergic radioligand in cardiac imaging.


METHODS
Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac beta-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-(125)I-ICI-H from the silylated precursor 2-SiMe(3)-ICI-H was established. The specific activity was 80 GBq/ micro mol, the radiochemical yield ranged from 70 to 80%.


RESULTS
The unlabelled compound 2-I-ICI-H showed high beta(1)-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac beta-adrenoceptors. The radiolabelled counterpart 2-(125)I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac beta(1)-adrenoceptors in vivo.


CONCLUSIONS
Because of its high non-specific binding 2-(125)I-ICI-H is no suitable radiotracer for imaging in vivo.
Riemann
B
B
Department of Nuclear Medicine, Münster University, Germany. riemanb@uni-muenster.de
Law
M P
MP
Kopka
K
K
Wagner
St
S
Luthra
S
S
Pike
V W
VW
Neumann
J
J
Kirchhefer
U
U
Schmitz
W
W
Schober
O
O
Schäfers
M
M
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D006321:Heart / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D011412:Propanolamines / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C481040:2-I-ICI-H; D000319:Adrenergic beta-Antagonists; D001713:Biphenyl Compounds; D011412:Propanolamines; D019275:Radiopharmaceuticals; D018342:Receptors, Adrenergic, beta-1; C025716:ICI 89406; C033394:CGP 12177