title: Preparation and preliminary evaluation of 99mTc-EC-For-MLFK.
abstract: For-Met-Leu-Phe-Lys (For-MLFK), a chemotactic peptide that binds with high affinity to granulocytes and monocytes, was labeled with 99mTc using ethylene dicysteine (EC) as the metal chelating system. EC was selected because of the rapid renal excretion of its 99mTc-complex and therefore, was expected to enhance the degree of urinary elimination of the peptide-conjugate. 99mTc-EC-For-MLFK was prepared using a preformed chelate approach. After incubation of 99mTc-EC-For-MLFK with total blood, 68.1% of the labeled peptide was associated with WBC and 86% of this cell-associated activity was bound to granulocytes. Biodistribution studies in normal mice revealed a very fast blood clearance (4.1% and 0.6% of I.D. in blood at respectively 5 and 60 min p.i.). However, elimination of the labeled peptide proceeds mainly via the hepatobiliary system (24.5% of I.D. in liver and 48.8% of I.D. in intestines at 60 min p.i.) and to a much lower degree via the kidneys (17.9% in renal system at 60 min p.i.). From these results, it is concluded that 99mTc-EC-For-MLFK is not suited to image infections, despite its high binding to granulocytes, since it leads to high, non-specific, abdominal activity.
authors.affiliation: Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U. Leuven, B-3000 Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Verbeke
authors.forename: A
authors.initials: A
authors.lastname: Verbeke
authors.forename: H
authors.initials: H
authors.lastname: Vanbilloen
authors.forename: A
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D006098:Granulocytes / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D051379:Mice; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011869:Radioligand Assay / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C470856:technetium Tc 99m ethylene dicysteine-formyl-methionyl-leucyl-phenylalanyl-lysine