Assessment of radiolabeled stabilized F(ab')2 fragments of monoclonal antiferritin in nude mouse model.
The biodistribution of 111In-labeled stabilized fragments of monoclonal antiferritin was studied in nude mice bearing a human hepatoma tumor xenograft. Pharmacokinetics and tumor targeting of fragment Fab'-linker-Fab' fragment molecules (stabilized F(ab')2) were compared to unmodified F(ab')2 fragment molecules and immunoglobulin G (IgG). Significant differences were observed in tumor and normal organ uptake at 12, 24, 48 and 72 hr. Tumor retention of stabilized F(ab')2 fragments was approximately 2.5-fold higher than of unmodified F(ab')2 at 48 hr. Blood clearance for stabilized F(ab')2 was relatively faster than intact IgG, while unmodified F(ab')2 cleared more rapidly from the circulation. Kidney radioactivity of unmodified F(ab')2 was at least two times higher than kidney radioactivity of stabilized F(ab')2 at all time points. Stabilized F(ab')2 demonstrated 40% less liver uptake than intact IgG. In these studies with nude mice, substantial retention of stabilized F(ab')2 in tumor and significant reduction in liver and kidney uptake of these fragments indicated that they could also have a higher therapeutic ratio than IgG or unmodified F(ab')2 in human patients.
Quadri
S M
SM
Department of Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Lai
J
J
Mohammadpour
H
H
Vriesendorp
H M
HM
Williams
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D005293:Ferritins / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007128:Immunoglobulin Fragments; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007205:Indium Radioisotopes; D005293:Ferritins