Protoporphyrin IX fluorescence induced in basal cell carcinoma by oral δ-aminolevulinic acid

Limited depth of penetration significantly limits photodynamic therapy of nodular basal cell carcinoma (BCC) using topical delta(5)-aminolevulinic acid (ALA), To demonstrate safety and efficacy of orally administered ALA in inducing endogenous protoporphyrin IX (PpIX) production in BCC, 13 patients with BCC ingested ALA in a dose-escalation protocol, All dose ranges (10, 20 or 40 mg/kg single doses) resulted in formation of PpIX in human skin and BCC, measurable by in vivo fluorescence spectrophotometry, The PpIX fluorescence peaked in tumors before normal adjacent skin from 1 to 3 h after ALA ingestion, Gross fluorescence imaging of ex vivo specimens revealed greater PpIX fluorescence in tumor than normal skin only at the 40 mg/kg dose, Fluorescence microscopy confirmed this finding by showing distinct, full-thickness PpIX fluorescence in all subtypes of BCC only after ALA given at 40 mg/kg, Side effects were dose dependent and self limited, Photosensitivity lasting less than 24 h and nausea coinciding with peak skin PpIX fluorescence occurred at 20 and 40 mg/kg doses, After 10 mg/kg ALA, serum hepatic enzyme levels rose to a maximum within 24 h, then resolved over 13 weeks, Transient bilirubinuria occurred in two patients.