Biodistribution of a benzoporphyrin derivative-monoclonal antibody conjugate in A549-tumor-bearing nude mice.
Biodistribution of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD) was compared in DBA/2 mice bearing the syngeneic M-1 tumor and nude mice bearing the A549 human squamous cell carcinoma. These studies, using internally labeled 14C-BPD showed that in general, biodistribution between the two strains was equivalent with the exception of two tissues; lymph nodes (BPD levels were higher in nude mice) and tumor (BPD levels were lower in nude mice). Further studies were carried out in A549-tumor-bearing nude mice in which the biodistribution of BPD conjugated to a monoclonal antibody (5E8) with specificity for an antigen on A549 cells was compared to a conjugate prepared with an irrelevant monoclonal antibody (T48). These studies showed that both conjugates had biodistribution characteristics which distinguished them from free BPD in that they remained in the circulation and most tissues for significantly longer times than did free BPD. Also, with the exception of the 5E8-BPD conjugate and A549 tumor tissue, levels in all tissues were highest at the 3-h time point following injection of conjugates. In the case of A549 tumor and the 5E8-BPD conjugate the highest concentration of 14C-labeled material was observed at the 14-h time point following injection. The results reported herein show that the conjugates tested behaved differently from free BPD, indicating that the materials did not become dissociated in vivo and that the specific conjugate (5E8-BPD) demonstrated specificity for the A549 tumor in terms of the kinetics of its accumulation in tumor tissue.
Department of Microbiology, University of British Columbia, Vancouver, Canada.
F N
FN
Jiang
A M
AM
Richter
A K
AK
Jain
J G
JG
Levy
C
C
Smits
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism*; D004337:Drug Carriers; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D