Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies.
We describe 2-step and 3-step strategies for intraperitoneal tumor radio-localization by means of monoclonal antibodies (MAbs). Nude mice bearing intraperitoneal human colon carcinoma tumors were injected i.p. with biotinylated MAb AUAI, followed 24 hr later by radioiodinated streptavidin (2-step). The uptake of radioactivity in tumor and normal tissues was measured 4 hr after injection of radioactive compound. A 3-step strategy consisted in administering biotinylated antibody, cold avidin after 24 hr and 111In-labelled biotin after a further 4 hr; mice were then killed 2 hr later. Tumor localization of intraperitoneally-administered biotinylated antibody and direct targeting of radioactive streptavidin to biotinylated antibody bound to tumor sites were demonstrated using immunohistochemistry and autoradiography. Our results show that (i) the 2-step approach increased the percentage of radioactivity uptake by tumor with respect to directly labelled antibodies (24% vs. 6%) and improved the tumor/non-tumor ratio; (ii) the 3-step approach allowed faster blood clearance of the radioactive probe (111In-biotin) and yielded high tumor/non-tumor ratios. "Pre-targeting" methods appear to have advantages over the conventional 1-step approach with directly radiolabelled antibody.
Paganelli
G
G
Ospedale M. Bufalini, Cesena, Italy.
Pervez
S
S
Siccardi
A G
AG
Rowlinson
G
G
Deleide
G
G
Chiolerio
F
F
Malcovati
M
M
Scassellati
G A
GA
Epenetos
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001345:Autoradiography; D001360:Avidin / Q000008:administration & dosage / Q000633:toxicity; D001426:Bacterial Proteins / Q000008:administration & dosage; D001710:Biotin / Q000008:administration & dosage; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D007150:Immunohistochemistry; D007205:Indium Radioisotopes / Q000008:administration & dosage; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019809:Streptavidin; D013997:Time Factors; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D001360:Avidin; D001710:Biotin; D019809:Streptavidin