TY - JOUR
T1 - Gamma imaging with negatively charge-modified monoclonal antibody
T2 - Modification with synthetic polymers
AU - Khaw, B. A.
AU - Klibanov, A.
AU - O'Donnell, S. M.
AU - Saito, T.
AU - Nossiff, N.
AU - Slinkin, M. A.
AU - Newell, J. B.
AU - Strauss, H. W.
AU - Torchilin, V. P.
PY - 1991
Y1 - 1991
N2 - Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure. The isoelectric points (PI) of unmodified antimyosin (AM) Fab (PI range 7-9, M(r) = 52kD) were changed to PIs predominantly between 4 and 5 (M(r) = 59 kD for DTPA-PL(3.3kD)-AM-Fab and 67kD for DTPA-PL(17kD)-AM-Fab). These AM-Fab preparations were tested for specific target localization and visualization in vivo in an experimental canine model of acute myocardial infarction. The charge-modified 111In-labeled AM-Fab preparations showed enhanced target (necrotic myocardium) visualization within 30 min of intravenous infusion and decreased background activity in normal myocardium (mean %ID/g ± s.e.m., 0.0076 ± 0.0006, n = 164, and 0.0056 ± 0.0004, n = 92, for 111In-DTPA-PL(3.3kD)- and DTPA-PL(17kD)-AM-Fab respectively) relative to conventional 111In-DTPA-AM-Fab (0.0263 ± 0.0037, n = 135) (p < 0.001) or radioiodinated AM-Fab (0.0098 ± 0.0006, n = 256) (p ≤ 0.001). Furthermore, the concentration of negatively charged 111In-labeled antimyosin Fab decreased in non-target organs such as the liver and kidneys. In diagnostic and therapeutic applications, charge-modified macromolecules may improve target localization and reduce non-target organ activity.
AB - Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure. The isoelectric points (PI) of unmodified antimyosin (AM) Fab (PI range 7-9, M(r) = 52kD) were changed to PIs predominantly between 4 and 5 (M(r) = 59 kD for DTPA-PL(3.3kD)-AM-Fab and 67kD for DTPA-PL(17kD)-AM-Fab). These AM-Fab preparations were tested for specific target localization and visualization in vivo in an experimental canine model of acute myocardial infarction. The charge-modified 111In-labeled AM-Fab preparations showed enhanced target (necrotic myocardium) visualization within 30 min of intravenous infusion and decreased background activity in normal myocardium (mean %ID/g ± s.e.m., 0.0076 ± 0.0006, n = 164, and 0.0056 ± 0.0004, n = 92, for 111In-DTPA-PL(3.3kD)- and DTPA-PL(17kD)-AM-Fab respectively) relative to conventional 111In-DTPA-AM-Fab (0.0263 ± 0.0037, n = 135) (p < 0.001) or radioiodinated AM-Fab (0.0098 ± 0.0006, n = 256) (p ≤ 0.001). Furthermore, the concentration of negatively charged 111In-labeled antimyosin Fab decreased in non-target organs such as the liver and kidneys. In diagnostic and therapeutic applications, charge-modified macromolecules may improve target localization and reduce non-target organ activity.
UR - http://www.scopus.com/inward/record.url?scp=0025908687&partnerID=8YFLogxK
M3 - Article
C2 - 1880577
AN - SCOPUS:0025908687
SN - 0161-5505
VL - 32
SP - 1742
EP - 1751
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 9
ER -