Use of isothiocyanatobenzyl-DTPA derivatized monoclonal antimyosin fab for enhanced in vivo target localization.
Monoclonal antimyosin Fab (AM-Fab) was radiolabeled with 111In via a new bifunctional chelating agent, isothiocyanatobenzyl-DTPA (SCN-DTPA), and used to visualize acute reperfused experimental myocardial infarction. Antibody localization was compared to 201Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of 111In-SCN-DTPA AM-Fab preparations (Prep 1 [n = 5] and 2 [n = 4]). The biodistribution was compared to that of 111In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). 111In-SCN-DTPA AM-Fab Prep 1 (lowest specific activity) showed highest specific target localization (31.6 +/- 3.5, MEAN infarct[0-20% Tl-201] to normal ration +/- SE) and lowest hepatic sequestration (0.0108 +/- 0.002% ID/g). Prep 2 showed similar infarct localization (18.4 +/- 1.2) to control 111In-DTPA AM-Fab (16.9 +/- 1.1), but had higher hepatic activity (0.0326 +/- 0.014 and 0.0267 +/- 0.006 respectively). This difference in in vivo localization occurred despite the lack of changes in in vitro immunoreactivities of the AM-Fab preparations. The enhanced target localization with minimal hepatic activity may permit a more sensitive diagnostic application of 111In-labeled AM-Fab in future clinical studies.
Khaw
B A
BA
Department of Nuclear Medicine, Massachusetts General Hospital, Boston.
Gansow
O
O
Brechbiel
M W
MW
O'Donnell
S M
SM
Nossiff
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D002614:Chelating Agents; D004285:Dogs; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D009203:Myocardial Infarction / Q000000981:diagnostic imaging*; D009218:Myosins / Q000276:immunology*; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; C054343:1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid; D004369:Pentetic Acid; D009218:Myosins