Tumour localization of uroporphyrin isomers I and III and their correlation to albumin and serum protein binding

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Abstract
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 μM 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. We conclude, (i) that serum proteins, particularly albumin, may play a significant role in governing the localization of P in tissues and, (ii) UROP clinically is ideally suited as a diagnostic marker of pre‐ or early mucosal malignancy as minimal retention by skin and gut would increase fluorescence specificity and diminish photocutaneous side effects.