title: Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema.
abstract: The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.
authors: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.
authors: Srivalleesha
authors: S
authors: Mallidi
authors: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.
authors: Sriram
authors: S
authors: Anbil
authors: Physical Sciences Inc., Andover, Massachusetts 01810.
authors: Seonkyung
authors: S
authors: Lee
authors: Massachusetts General Hospital, Department of Dermatology, Boston, Massachusetts 02114.
authors: Dieter
authors: D
authors: Manstein
authors: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.
authors: Stefan
authors: S
authors: Elrington
authors: Massachusetts General Hospital, Department of Dermatology, Boston, Massachusetts 02114.
authors: Garuna
authors: G
authors: Kositratna
authors: Massachusetts General Hospital, Biostatistics Department, Boston, Massachusetts 02114.
authors: David
authors: D
authors: Schoenfeld
authors: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755.
authors: Brian
authors: B
authors: Pogue
authors: Physical Sciences Inc., Andover, Massachusetts 01810.
authors: Steven J
authors: SJ
authors: Davis
authors: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.
authors: Tayyaba
authors: T
authors: Hasan
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000494:pharmacology; D004890:Erythema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D026082:Singlet Oxygen / Q000032:analysis* / Q000737:chemistry; D012867:Skin / Q000187:drug effects; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D026082:Singlet Oxygen; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX