title: The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device.
abstract: Topical protoporphyrin (PpIX)-induced photodynamic therapy (PDT) relies on the penetration of the prodrug into the skin lesion and subsequent accumulation of the photosensitizer. Methyl aminolevulinate (MAL)-PDT is an established treatment for thinner and superficial non-melanoma skin cancers (NMSCs) but for the treatment of the thicker nodular basal cell carcinoma (nBCC) enhanced penetration of the prodrug is required. This study employed a new higher pressure, oxygen pressure injection (OPI) device, at the time of Metvix® application with a view to enhancing the penetration of MAL into the tumors. Each patient had Metvix® applied to a single nBCC followed by application of a higher pressure OPI device. Following different time intervals (0, 30, 60, 120 or 180 min) the tumors were excised. The maximum depth and area of MAL penetration achieved in each lesion was measured using PpIX fluorescence microscopy. As expected, an increase in the depth of MAL-induced PpIX accumulation and area of tumor sensitized was observed over time; when the Metvix® cream was applied for 0, 30, 60, 120 and 180 min the median depth of PpIX fluorescence was 0%, 21%, 26.5%, 75.5% and 90%, respectively and the median area of tumor sensitized was 0%, 4%, 6%, 19% and 60%, respectively. As the investigation presented here did not include a control arm, the relative depths of fluorescence observed in this study were statistically compared (using the non-parametric Mann Whitney U test) with the results of our previous study where patients had Metvix® cream applied either with or without the standard pressure OPI device. When the higher pressure OPI device was employed compared to without OPI this increase was observed to be greater following 30, 120, and 180 min although overall not significantly (p=0.835). In addition, no significant difference between the higher pressure OPI device employed here and the previously investigated standard pressure OPI device was observed (p=0.403). However, when the results for both OPI devices were combined and compared to the standard treatment (no OPI employed) group, although the difference did not reach significance (p=0.531) a consistent and substantial increase in the depth of PpIX fluorescence was observed, therefore employment of an OPI device during topical MAL-PDT protocols warrants further investigation as a technique for enhancing MAL penetration.
authors.affiliation: Clinical Photobiology, European Centre for Environment and Human Health, Peninsula Medical School, University of Exeter, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK. emma.blake@pms.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Blake
authors.forename: S
authors.initials: S
authors.lastname: Campbell
authors.forename: J
authors.initials: J
authors.lastname: Allen
authors.forename: J
authors.initials: J
authors.lastname: Mathew
authors.forename: P
authors.initials: P
authors.lastname: Helliwell
authors.forename: A
authors.initials: A
authors.lastname: Curnow
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D001692:Biological Transport; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000628:therapy; D007267:Injections / Q000295:instrumentation*; D010100:Oxygen / Q000378:metabolism*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism; D011312:Pressure; D011355:Prodrugs / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000628:therapy; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D010100:Oxygen