Biodistribution of charged F(ab')₂ photoimmunoconjugates in a xenograft model of ovarian cancer

The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorin(e6) c(e6) was attached site specifically to the F(ab')₂, fragment of the murine monoclonal antibody OC125, directed against human ovarian cancer cells, via poly-1-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with ¹²⁵I and compared with non-specific rabbit IgG PICs after intraperitoneal (i.p.) injection into nude mice. Samples were taken from normal organs and tumour at 3 h and 24 h. Tumour to normal ¹²⁵I ratios showed that the cationic OC125F(ab')₂ PIC had the highest tumour selectivity. Ratios for c(e6) were uniformly higher than for ¹²⁵I, indicating that c(e6) became separated from ¹²⁵I. OC125F(ab')₂ gave highest tissue values of ¹²⁵I, followed by cationic OC125F(ab')₂ PIC; other species were much lower. The amounts of c(e6) delivered per gram of tumour were much higher for cationic OC125F(ab')₂, PIC than for other species. The results indicate that cationic charge stimulates the endocytosis and lysosomal degradation of the OC125F(ab')₂-pl-c(e6) that has bound to the i.p. tumour. Positively charged PICs may have applications in the i.p. photoimmunotherapy of minimal residual ovarian cancer.