Long-term biodistribution in tumored mice of murine and chimeric B72.3-IgG antibody radiolabeled with 114mIn via both DTPA and a macrocyclic chelator.
To assess the possibilities of using 114mIn as a therapeutic agent, the long-term biodistribution of 114mIn was studied, in tumor-bearing nude mice, after injection of labeled monoclonal antibody (MoAb) B72.3 IgG, either DTPA-coupled murine, DTPA-coupled chimeric, or macrocycle-coupled chimeric antibody. Although the biodistributions in all cases were similar, there were important differences. The use of DTPA-coupled chimeric antibody led to higher concentrations of radioactivity in tumor, and to lower concentrations in liver and bone, as compared to DTPA-coupled murine antibody. The use of macrocycle-coupled chimeric antibody led to higher concentrations of radioactivity in the liver and in bone as compared to the DTPA-coupled chimeric antibody. However, in this case there were no significant differences in tumor uptake or clearance. Radiation doses were calculated based on the organ retention and by neglecting source-to-target contributions. Radiation dose distribution was marginally favorable for therapy in the group injected with DTPA-coupled chimeric antibody.
Aas
M
M
Department of Nuclear Medicine, University of Massachusetts Medical Center, Worcester 01655.
Mardirossian
G
G
Griffin
T W
TW
Salimi
A R
AR
Ito
T
T
Bushe
H S
HS
Atcher
R W
RW
Hines
J J
JJ
Brill
A B
AB
Hnatowich
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001345:Autoradiography; D002460:Cell Line; D002614:Chelating Agents; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000532:radiotherapy; D004369:Pentetic Acid; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007205:Indium Radioisotopes; D004369:Pentetic Acid