Biodistribution of charged 17.1A photoimmunoconjugates in a murine model of hepatic metastasis of colorectal cancer

Optimizing photodynamic therapy involves attempting to increase both the ab solute tumour content of photosensitizer and the selectivity between tumour and surrounding normal tissue. One reason why photodynamic therapy has not been considered suitable for treatment of metastatic tumours in the liver, is the poor selectivity of conventional photosensitizers for tumour compar ed to normal liver. This report details an alternative approach to increasi ng this selectivity by the use of antibody-targeted photosensitizers (or ph otoimmunoconjugates) to target intrahepatic tumours caused by human colorec tal cancer cells in the nude mouse, and explores the role of molecular char ge on the tumour-targeting efficiency of macromolecules. The murine monoclo nal antibody 17.1A (which recognizes an antigen expressed on HT 29 cells) w as used to prepare site-specific photoimmunoconjugates with the photosensit izer chlorine6. The conjugates had either a predominant cationic or anionic charge and were injected i.v. into tumour-bearing mice. Biodistribution 3 or 24 h later was measured by extraction of tissue samples and quantitation of chlorine6 content by fluorescence spectroscopy. The photoimmunoconjugat es were compared to the polylysine conjugates in an attempt to define the e ffect of molecular charge as well as antibody targeting. The anionic 17.1A conjugate delivered more than twice as much photosensitizer to the tumour a t 3 h than other species (5 times more than the cationic 17.1A conjugate) a nd had a tumour:normal liver ratio of 2.5. Tumour-to-liver ratios were grea ter than one for most compounds at 3 h but declined at 24 h. Tumour-to-skin ratios were high (> 38) for all conjugates but not for free chlorines. Cat ionic species had a high uptake in the lungs compared to anionic species. T he photoimmunoconjugates show an advantage over literature reports of other photosensitizers, which can result in tumour:normal liver ratios of less t han 1. (C) 2000 cancer Research Campaign http://www.bjcancer.com.