Fluorescence diagnosis of bladder cancer: a novel in vivo approach using 5-aminolevulinic acid (ALA) dendrimers

OBJECTIVE To overcome the relative lack of tumour selectivity of fluorescence-guided cystoscopy using 5-aminolevulinic acid (ALA) or its ester derivative (e. g. hexylaminolevulinate, h-ALA; Hexvix (R)), we evaluated the use of dendrimers bearing different ALA loads in rats bearing orthotopic bladder tumours. MATERIALS AND METHODS Rat bladders were instilled with h-ALA or ALA dendrimers and fluorescence ratio between tumour and normal urothelium, as well as tumour and muscle and depth of fluorescence were determined with Image J software. Quantification of ALA and/or esters systemic reabsorption was evaluated by high-performance liquid chromatography. RESULTS Slow hydrolysis of ALA from dendrimers as observed in vitro implies a higher initial ALA load and longer resting times in vivo. Sustained synthesis of protoporphyrin IX (PpIX) explains persistence of fluorescence for >24 h. There were significantly better fluorescence ratios with dendrimers, as well as higher penetration depths and absence of systemic reabsorption. CONCLUSION The prolonged and sustained PpIX synthesis, the improved tumour selectivity with a deeper penetration and the absence of systemic reabsorption are primary indicators that ALA dendrimers could be an alternative to h-ALA in fluorescence-guided cystoscopy.