Combination radioimmunotherapy with local hyperthermia: increased delivery of radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts.
Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.
Department of Nuclear Medicine, Kanazawa University School of Medicine, Japan. kinuya@med.kanazawa-u.ac.jp
S
S
Kinuya
K
K
Yokoyama
T
T
Hiramatsu
H
H
Tega
K
K
Tanaka
S
S
Konishi
N
N
Shuke
T
T
Aburano
N
N
Watanabe
T
T
Takayama
T
T
Michigishi
N
N
Tonami
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018796:Immunoconjugates; D007457:Iodine Radioisotopes