Biodistribution of Charged F(ab')2 Photoimmunoconjugates in a Xenograft Model of Ovarian Cancer
View/ Open
brjcancer00183-0063.pdf (1.433Mb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.Published Version
https://doi.org/10.1038/bjc.1997.149Metadata
Show full item recordCitation
Duska, LR, MR Hamblin, MP Bamberg, and T Hasan. 1997. “Biodistribution of Charged F(ab’)2 Photoimmunoconjugates in a Xenograft Model of Ovarian Cancer.” British Journal of Cancer 75 (6): 837–44. https://doi.org/10.1038/bjc.1997.149.Abstract
The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorine(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-l-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with I-125 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 I-125 ratios showed that the cationic OC125F(ab')(2) PIC had the highest tumour selectivity. Ratios for c(e6) were uniformly higher than for I-125, indicating that c(e6) became separated from I-125. OC125F(ab')(2) gave highest tissue values of I-125, 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.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41200899
Collections
- HMS Scholarly Articles [18278]
Contact administrator regarding this item (to report mistakes or request changes)