title: Uptake of radiolabeled morphiceptin and its analogs by experimental mammary adenocarcinoma: in vitro and in vivo studies.
abstract: Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) and its analogs modified at position 3: [D-Phe(3)]morphiceptin, [D-ClPhe(3)]morphiceptin and [D-Cl(2)Phe(3)]morphiceptin were synthesized and labeled with [(125)I] or [(131)I]. Their binding to membranes isolated from experimental adenocarcinoma was examined in vitro with the use of a cross-linking assay followed by the Western blot technique. The radioactive complex had molecular weight of about 65 kDa and was detectable by anti-mu-opioid receptor polyclonal antibody. Expression of the mu-opioid receptor in mouse mammary adenocarcinoma was confirmed by reverse transcriptase-polymerase chain reaction. The binding studies showed the highest affinity and capacity for [D-Phe(3)]morphiceptin (K(d) 0.39 and B(max) 1112) and [D-ClPhe(3)]morphiceptin (K(d) 1.8 and B(max) 220). Morphiceptin and its D-Cl(2)Phe analog had significantly lower B(max) values (131 and 83, respectively). Biodistribution experiments in tumor-bearing C3H/Bi mice with the use of the (131)I-labeled peptides confirmed the results of our in vitro studies. The highest accumulation of radioactive peptides in the tumor tissue was also found for peptides with D-Phe and D-ClPhe.
authors.affiliation: Department of Pharmaceutical Biochemistry, Molecular Biology Laboratory, Medical University, Muszynskiego Street 1, 90-151 Lodz, Poland. mirowski@ich.pharm.am.lodz.pl
authors.forename: M
authors.initials: M
authors.lastname: Mirowski
authors.forename: R
authors.initials: R
authors.lastname: Wiercioch
authors.forename: A
authors.initials: A
authors.lastname: Janecka
authors.forename: E
authors.initials: E
authors.lastname: Balcerczak
authors.forename: E
authors.initials: E
authors.lastname: Byszewska
authors.forename: G
authors.initials: G
authors.lastname: Birnbaum
authors.forename: Sz
authors.initials: S
authors.lastname: Byzia
authors.forename: P
authors.initials: P
authors.lastname: Garnuszek
authors.forename: R
authors.initials: R
authors.lastname: Wierzbicki
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D000818:Animals; D004723:Endorphins / Q000493:pharmacokinetics*; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008809:Mice, Inbred C3H; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004723:Endorphins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu; C028889:morphiceptin