Dosimetry model for photodynamic therapy with topically administered photosensitizers.
OBJECTIVE
Photodynamic therapy (PDT) based on topical application of photosensitizers has been under development over the last years. Typical applications are treatment of basal cell carcinoma of the skin and photoablation of the endometrium. The dosimetry for topically administered photosensitizers must take a time-dependent inhomogenous drug distribution into account together with the conventional parameters such as optical scattering, absorption, and photobleaching.


METHODS
This study presents a dosimetry model where the cytotoxic dose is calculated in a stepwise procedure. The first step calculates the time-dependent distribution of 5-aminolevulinic acid (5-ALA) from diffusion theory. In skin this distribution is dependent on drug permeability through the stratum corneum, on the diffusivity of dermis and epidermis, on the drug clearance time, and on the conversion rate from 5-ALA to protoporphyrin IX (PpIX). In the second step the distribution of PpIX is calculated from the 5-ALA distribution found in the first step taking the dynamics of the biosynthesis of 5-ALA to PpIX and the clearance time of PpIX into account. In the third step the generation of cytotoxic singlet oxygen is calculated from the optical distribution during irradiation, taking a photobleaching mechanism into account.


RESULTS
The distribution of cytotoxic oxygen is predicted from the optical dose, the drug dose, and the time between the application of the drug and the irradiation.


CONCLUSIONS
The presented dosimetry model is made as simple as possible, yet composite enough to enable all relevant parameters to be taken into account. The model that is based on a linear theory in a semi-infinite medium can, if required, be extended to take nonuniform and nonlinear phenomena into account.
Svaasand
L O
LO
Norwegian Institute of Technology, Trondheim, Norway.
Wyss
P
P
Wyss
M T
MT
Tadir
Y
Y
Tromberg
B J
BJ
Berns
M W
MW
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D004285:Dogs; D008954:Models, Biological; D055095:Optics and Photonics; D010100:Oxygen / Q000378:metabolism; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011355:Prodrugs / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism
D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D010100:Oxygen