Tumour localization of uroporphyrin isomers I and III and their correlation to albumin and serum protein binding.
We were the first to report the superiority of uroporphyrin I (UROP I) as a tumour localizer when compared to haematoporphyrin derivative (HPD). In this study, we compared both isomers of UROP, i.e. I and III, in a KHJJ mammary carcinoma mouse model. Six and 18 h after UROP administration, the tumour, skin and gut porphyrin (P) content was quantitated. Tumour UROP I levels were always at least 50% higher than UROP III in tumour, whereas both isomers were barely detectable in the skin and gastrointestinal tract. We then explored the possibility that tumour P uptake might relate in part to the affinity of circulating P to mouse serum proteins (MSP), in particular, the major binding protein constituent, albumin. Copro-P III, deutero-P 2,4 disulphonic acid (DP), proto-P IX (PP) and heptacarboxylic P I (Hepta I) which in our mouse tumour model do not localize in malignant tissue, were compared to UROP I and III. The P was mixed with 0.775 microM human serum albumin (HSA) at different molar ratios (HSA:P range 2-8) and the unbound P concentration quantitated using an Amicon CF-25 membrane cone with centrifugation. The percentage free P was significantly higher for UROP I (92-98%) than III (82-95%) and significantly more than that observed with non-tumour localizing P studied. Similar data were obtained with MSP. This is consistent with the notion that enhanced uptake and retention (particularly UROP I) by malignant neoplastic tissue might reflect a higher affinity for UROP by tumour constituents than by circulating proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011166:Porphyrins / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D014578:Uroporphyrins / Q000378:metabolism*
D001798:Blood Proteins; D011166:Porphyrins; D012709:Serum Albumin; D014578:Uroporphyrins; C022181:uroporphyrin III; C034103:uroporphyrin I