Blood distribution and plasma protein binding of PHOTOCYANINE: a promising phthalocyanine photosensitizer inphaseII clinical trials

Blood distribution and plasma protein binding are the important properties that can influence pharmacokinetics and ultimately the anticancer efficacy of photosensitizers in clinical photodynamic therapy. As a novel and promising phthalocyanine photosensitizer under clinical phase II investigation in China, the superiority of PHOCYANINE is speculated on its attribution to its binding with plasma proteins. To verify this hypothesis, explore the targeting mechanism and further apply foundation for its clinical trial evaluation, we further study its in vitro and in vivo human blood distribution, in vitro plasma protein and lipoprotein binding in detail. PHOTOCYANINE was found to be mainly distributed in plasma with low K BP and K EP values. Moreover, its high binding rates to plasma proteins among various species (mouse, rat, dog, monkey, and human) were then determined. Among these plasma proteins, human serum albumin and al-acid-glycoprotein were found to bind PHOTOCYANINE highly, and low-density lipoproteins have the highest percentage of PHOTOCYANINE over other lipoproteins. This study is expected to provide some guidance for PDT clinical evaluations and for further molecular design and development of photosensitizers.