title: Lowering of pI by acylation improves the renal uptake of 99mTc-labeled anti-Tac dsFv: effect of different acylating reagents.
abstract: Anti-Tac disulfide-stabilized variable region fragment (dsFv) was labeled with 99mTc by a preformed chelate approach using 99mTc-MAG3-trifluorophenyl (TFP) ester. Simultaneously it was acylated with TFP-lactate or succinic anhydride to decrease the isoelectric point of dsFv (pI 10). Acylation of dsFv (0.04 mM) with the lactate at a 73 times molar excess reduced the pI to 5.0-6.7, whereas acylation with succinic anhydride at a 30 times molar excess reduced the pI to 4.9-8.7. Comparative biodistribution studies performed in mice (n = 5) showed the reduced renal accumulation of the 99mTc proportional to the pI reduction. The effect of the pI on the reduced renal uptake was especially pronounced at 15 min postinjection. The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv.
authors.affiliation: Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA.
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Tae M
authors.initials: TM
authors.lastname: Yoo
authors.forename: Meyong-kon
authors.initials: MK
authors.lastname: Kim
authors.forename: Nhat
authors.initials: N
authors.lastname: Le
authors.forename: Eui-sik
authors.initials: ES
authors.lastname: Han
authors.forename: Q C
authors.initials: QC
authors.lastname: Wang
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
mesh_terms: D000215:Acylation; D000665:Ampholyte Mixtures / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000493:pharmacokinetics*; D001822:Body Burden; D005260:Female; D007526:Isoelectric Point; D007553:Isotope Labeling / Q000379:methods*; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D007773:Lactates / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013386:Succinates / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D000665:Ampholyte Mixtures; D000911:Antibodies, Monoclonal; D007773:Lactates; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013386:Succinates; C104214:technetium-99m-MAG3-dsFV