Protoporphyrin IX fluorescence induced in basal cell carcinoma by oral delta-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 40 mg/kg ALA, serum hepatic enzyme levels rose to a maximum within 24 h, then resolved over 1-3 weeks. Transient bilirubinuria occurred in two patients.
Tope
W D
WD
Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA. topex001@gold.tc.umn.edu
Ross
E V
EV
Kollias
N
N
Martin
A
A
Gillies
R
R
Anderson
R R
RR
D000284:Administration, Oral; D000622:Aminolevulinic Acid / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000378:metabolism*; D004347:Drug Interactions; D005453:Fluorescence; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX