Radioimmunotherapy of micrometastases in lung with vascular targeted Bi-213

A model system has been used to test the efficacy of vascular targeting of alpha-particle emitter Bi-213 for therapy of small, 'artificial' metastases in mouse lung. Specific monoclonal antibody (mAb) 201B was used to deliver greater than 30% of the injected dose to lung where tumours had developed due to intravenous injection of cells. Specific Bi-213-mAb 201B treatment o f BALB/c mammary carcinoma EMT-6 tumours in lung resulted in a dose-depende nt destruction of tumours and an extended lifespan of treated animals relat ive to controls, Significant reduction of lung tumour burden was noted in a nimals treated with 0.93 MBq injected dose or as little as 14 Gy absorbed d ose 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 gro wing 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 t reated with specific, labelled mAb relative to those in animals treated wit h control Bi-213 MAb or EDTA complexed Bi-213. Tumours treated in immunodef icient SCID mice were partially destroyed or at least retarded in growth, b ut ultimately regrew and proved fatal, indicating that an intact immune fun ction is necessary for complete cure. The data show that the short-lived al pha-particle emitter Bi-213 can be effectively targeted to lung blood vesse ls and that tumour cells growing in the lung are killed. The mechanism may involve direct killing of tumour cells from alpha-particle irradiation, kil ling through destruction of blood supply to the tumour, or a combination of the two.