Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysisin vivo

Abstract

Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.