Photodynamic therapy of human Barrett's cancer using 5-aminolaevulinic acid-induced protoporphyrin IX: an in-vivo dosimetry study in athymic nude mice.
OBJECTIVE
There has been a dramatic increase in recent years in the incidence of Barrett's oesophagus and the oesophageal adenocarcinoma associated with it. Alongside surgical treatment for early Barrett's carcinomas, endoscopic treatment procedures such as photodynamic therapy (PDT), which have much lower complication and mortality rates, will play an increasing role in the future. In this study, the effects of light energy dose, light fractionation and oxygenation on the efficacy of PDT were investigated for the first time in an in-vivo nude mice tumour model bearing a human Barrett's carcinoma.


METHODS
A total of 387 NMRI strain (nu/nu) nude mice with thymic aplasia (total 53 controls) were transplanted with human Barrett's carcinoma and treated with laser light at 635 nm (light dose 0-200 J/cm2, fluence rate 400 mW/cm2). 5-Aminolaevulinic acid-induced protoporphyrin IX (5-ALA-PpIX) (100 mg 5-ALA/kg body weight administered orally) was used as the photosensitizer.


METHODS
Fractionation studies were performed at 0, 50, 100 and 150 J/cm2. The light dose was administered in four equal fractions divided by three irradiation-free intervals of 120 s. Oxygenation studies were carried out at 150 J/cm2 with simultaneous oxygen supply of 2, 6 and 8 l oxygen/min.


RESULTS
Dosimetry studies demonstrated a positive correlation between increase in light dose and tumour destruction up to 150 J/cm2 when using either continuous or fractionated light delivery. The optimal light energy dose was 150 J/cm2. Neither fractionation of light nor simultaneous oxygenation enhanced the efficacy of the PDT.


CONCLUSIONS
This is the first study in the literature that proves the efficiency of PDT with 5-ALA-PpIX in human Barrett's adenocarcinoma and that demonstrates an exact dosimetry of the optimal light energy dose (150 J/cm2). No general recommendation can be made for the use of fractionation or oxygenation in clinical PDT.
Pech
Oliver
O
Department of Medicine II, HSK Wiesbaden, Wiesbaden, Germany.
Nagy
Christian D
CD
Gossner
Liebwin
L
May
Andrea
A
Ell
Christian
C
D000230:Adenocarcinoma / Q000188:drug therapy*; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D001471:Barrett Esophagus / Q000188:drug therapy*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000627:therapeutic use*; D011874:Radiometry
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX