Radioimmunotherapy of micrometastases in lung with vascular targeted 213Bi.
A model system has been used to test the efficacy of vascular targeting of alpha-particle emitter 213Bi for therapy of small, 'artificial' metastases in mouse lung. Specific monoclonal antibody (mAb) 201 B was used to deliver greater than 30% of the injected dose to lung where tumours had developed due to intravenous injection of cells. Specific 213Bi-mAb 201B treatment of BALB/c mammary carcinoma EMT-6 tumours in lung resulted in a dose-dependent destruction of tumours and an extended lifespan of treated animals relative to controls. Significant reduction of lung tumour burden was noted in animals treated with 0.93 MBq injected dose or as little as 14 Gy absorbed dose to the lung. Animals treated with higher doses (2.6-6.7 MBq) had nearly complete cure of lung tumours but eventually died of lung fibrosis induced by the treatment. Four other tumour cell types were studied: murine Line 1 lung carcinomas in syngeneic BALB/c mice, rat IC-12 tracheal carcinoma growing in severe combined immune deficient (SCID) mice, and two human tumours--epidermoid carcinoma A431 and lung carcinoma A549--growing in SCID mice. In all cases, the number of lung tumour colonies was reduced in animals treated with specific, labelled mAb relative to those in animals treated with control 213Bi MAb or EDTA complexed 213Bi. Tumours treated in immunodeficient SCID mice were partially destroyed or at least retarded in growth, but ultimately regrew and proved fatal, indicating that an intact immune function is necessary for complete cure. The data show that the short-lived alpha-particle emitter 213Bi can be effectively targeted to lung blood vessels and that tumour cells growing in the lung are killed. The mechanism may involve direct killing of tumour cells from alpha-particle irradiation, killing through destruction of blood supply to the tumour, or a combination of the two.
Kennel
S J
SJ
Life Sciences Division, Oak Ridge National Laboratory, TN 37831-6101, USA.
Boll
R
R
Stabin
M
M
Schuller
H M
HM
Mirzadeh
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D001729:Bismuth / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D008175:Lung Neoplasms / Q000098:blood supply / Q000532:radiotherapy* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008833:Microcirculation; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D051381:Rats; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D001729:Bismuth