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 δ( 5)- aminolevulinicacid ( ALA). To demonstrate safety and efficacy of orally administered ALAin inducing endogenous protoporphyrin IX(PpIX) production in BCC, 13 patients with BCC ingested ALAin 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 ALAingestion. 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 ALAgiven 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 40 mg/kg ALA, serum hepatic enzyme levels rose to a maximum within 24 h, then resolved over 1–3 weeks. Transient bilirubinuriaoccurred in two patients.