MONOCLONAL-ANTIBODY PO66 UPTAKE BY HUMAN LUNG-TUMORS IMPLANTED IN NUDE-MICE - EFFECT OF COADMINISTRATION WITH DOXORUBICIN

The efficacy of radioimmunotherapy of tumours with radiolabelled monoc lonal antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. In the case of MAbs d irected against intracellular antigens, increasing the permeability of the cytoplasmic membrane may augment the bioavailability of the antig en for the antibody. This raises the question whether the induction of tumour necrosis by chemotherapy can enhance the tumour uptake of radi olabelled monoclonal antibodies. In this work, the effect of doxorubic in on the biodistribution of Po66, an MAb directed against an intracel lular antigen, was studied in nude mice grafted with the human non-sma ll-cell lung carcinoma cell line SK-MES-1. After injection on day 0 of I-125-labelled Po66, tumour radioactivity increased up to days 3-5, a nd then remained unchanged to day 14. The combined administration of I -125-labelled Po66 with 8 mg kg(-1) doxorubicin, in two doses separate d by 7 days, doubled the radioactivity retained by the tumour. Histolo gical and historadiographic analysis showed, however, that the drug in duced cellular damage. In the absence of doxorubicin, the accumulation of Po66 was restricted to some necrotic areas, whereas with doxorubic in the necrosis was more extensive and the antibody more evenly distri buted. These results suggest that chemotherapy and immunoradiotherapy combined would enhance tumour uptake of radioisotope and promote more homogenous distribution of the radiolabelled MAb. This would promote e radication of the remaining drug-resistant cells in tumours.