Improved targeting of radiolabeled streptavidin in tumors pretargeted with biotinylated monoclonal antibodies through an avidin chase.
Radiolabeled streptavidin can be accumulated in tumors pretargeted with biotinylated anti-tumor antibodies. However, circulating biotinylated antibody and endogenous biotin may interfere with the tumor targeting of streptavidin. To reduce biotinylated antibody concentration in the blood, we injected avidin before streptavidin administration. The effects of avidin administration on the biodistribution and tumor targeting of radiolabeled streptavidin were examined.


METHODS
Biotinylated anti-human colon cancer monoclonal antibody (MAb) MLS128 was injected intravenously into nude mice bearing human colon cancer xenografts for pretargeting. After intraperitoneal injection of avidin, radioiodinated streptavidin was administered and its biodistribution and tumor accumulation was investigated.


RESULTS
Radioiodinated streptavidin specifically localized in the tumor pretargeted with biotinylated antibody. Avidin preadministration accelerated the tumor uptake and blood clearance of radioiodinated streptavidin. The tumor-to-blood radioactivity ratio at 6 and 24 hr after radiolabeled streptavidin injection were 1.23 +/- 0.29 and 3.04 +/- 0.86, respectively, in mice with avidin chase (mean +/- s.d., n = 7), and 0.82 +/- 0.17 and 2.29 +/- 0.29, respectively, in those without chase (mean +/- s.d., n = 7).


CONCLUSIONS
Localization of radiolabeled streptavidin in tumors pretargeted with biotinylated MAb could be improved by avidin chase. This approach may be useful for tumor radioimmunoimaging and radioimmunotherapy.
Yao
Z
Z
Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan.
Zhang
M
M
Kobayashi
H
H
Sakahara
H
H
Nakada
H
H
Yamashina
I
I
Konishi
J
J
D000818:Animals; D000911:Antibodies, Monoclonal; D001360:Avidin; D001426:Bacterial Proteins; D001710:Biotin; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D019809:Streptavidin
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007457:Iodine Radioisotopes; D001360:Avidin; D001710:Biotin; D019809:Streptavidin