title: Absence of binding of targeted analogs of somatostatin carrying cytotoxic radicals or radionuclides to growth hormone secretagogue receptors on human myocardium.
abstract: Various peripheral human tissues express receptors for growth hormone secretagogue (GHS), the highest density being in the myocardium. It was also reported that some octapeptide analogs of somatostatin (SRIH) can displace radiolabeled Tyr-Ala-hexarelin from GHS receptors on the human pituitary and heart. Thus, it is possible that radionuclide analogs of SRIH such as OctreoScan and recently developed cytotoxic SRIH analogs containing doxorubicin (DOX) intended for targeted tumor therapy, could bind to these GHS receptors, compromising the safety of compounds of this type. Therefore, we determined the binding of OctreoScan and two cytotoxic SRIH analogs consisting of octapeptide carrier RC-121 and DOX (AN-162) or 2-pyrrolino-DOX (AN-238) to human myocardium specimens. None of these compounds displayed specific binding to the human heart indicating that the clinical use of SRIH analogs linked to anthracyclines or radionuclides should not be associated with increased cardiac side effects.
authors.affiliation: Veterans Affairs Medical Center, New Orleans, LA 70112, USA.
authors.forename: Gabor
authors.initials: G
authors.lastname: Halmos
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Comaru-Schally
authors.forename: Attila
authors.initials: A
authors.lastname: Nagy
authors.forename: Anand
authors.initials: A
authors.lastname: Irimpen
mesh_terms: D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000368:Aged; D000814:Aniline Compounds / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000378:metabolism*; D011758:Pyrroles / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: C110845:AN 238; D000814:Aniline Compounds; D007205:Indium Radioisotopes; D011758:Pyrroles; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C000956:N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; D013004:Somatostatin; D015078:2-Hydroxyphenethylamine; D004317:Doxorubicin; C053408:RC 121; C081788:pentetreotide; D015282:Octreotide