In vivo efficacy of photodynamic therapy in three new xenograft models of human retinoblastoma.
OBJECTIVE
Retinoblastoma is the most common primary intraocular tumor in children. In industrialized countries, 95% of patients are cured by chemotherapy and conservative treatments. However, these treatments can increase the risk of secondary tumors in patients with a constitutional alteration of the RB1 gene. Photodynamic therapy represents a nonmutagenic therapeutic approach, and may reduce the incidence of secondary tumors. To study the in vivo efficacy of photodynamic therapy, human retinoblastoma xenografts were established in nude mice.


METHODS
Three xenografted cell lines, RB102-FER, RB109-LAK and RB111-MIL, were characterized and used for therapeutic evaluation. Mice were randomly divided into control and treatment groups with 5-8 mice in each group. Treatment groups received irradiation alone, photosensitizer alone or both in 2 of the 3 models and in the third model, photosensitizer plus irradiation was compared to untreated controls. mTHPC was injected intraperitoneally at a dose of 0.6mg/kg and verteporfin intravenously at a dose of 1mg/kg. Illuminations were performed 24h after mTHPC and 1h after verteporfin injections.


RESULTS
A transient but significant response to mTHPC was observed for RB102-FER (p=0.03) and a significant response to mTHPC for RB111-MIL (p<10(-4)) with partial regression maintained for more than 60 days. No significant difference between the different groups was observed for RB109-LAK, except in the verteporfin plus laser group (p=0.01).


CONCLUSIONS
The studies confirmed the suitability of the three xenograft models for the evaluation of photodynamic therapy in retinoblastoma. Our findings suggest that PDT may represent an alternative conservative treatment for these tumors.
INSERM U 612, Centre de Recherche, Institut Curie, 26 rue d'Ulm, 75 248 Paris Cedex 05, France. isabelle.aerts@curie.net
Isabelle
I
Aerts
Pascal
P
Leuraud
Jocelyne
J
Blais
Anne-Lise
AL
Pouliquen
Philippe
P
Maillard
Claude
C
Houdayer
Jérôme
J
Couturier
Xavier
X
Sastre-Garau
David
D
Grierson
François
F
Doz
Marie France
MF
Poupon
D000818:Animals; D045744:Cell Line, Tumor; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D000077362:Verteporfin
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C072269:temoporfin