23Na MRI longitudinal follow-up of PDT in a xenograft model of human retinoblastoma.
BACKGROUND
Photodynamic therapy is an established cancer treatment in which a photosensitizing agent is activated by exposure to light thus generating cytotoxic reactive oxygen species that cause cellular damage.


METHODS
A new photosensitizer synthesized at Curie Institute was used to treat retinoblastoma xenografts in mice, a glycoconjugated meso substituted porphyrin derivative, that showed some retinoblastoma cell affinity. The longitudinal follow-up of the tumors was carried out by (23)Na MRI (without adding exogenous contrast agents) to map the extracellular compartment and to characterize cell packing. Two regimens were followed to target either blood vessels alone or blood vessels and cancer cells simultaneously.


CONCLUSIONS
Only the protocol targeting both cancer cells and blood vessels effectively induces cellular death, confirmed by histology at the end of the experiment. Sodium MRI evidences a huge change in the cellular density of tumors only 24h after a double targeting (vascular and cellular) PDT treatment. We suggest that this change was possibly due to a bystander effect that can be promoted by the intercellular signaling favored by the high cellular density of retinoblastoma. These results indicate that non-invasive (23)Na imaging (which detects the tumor response to treatment from very early stages) in association with non-mutagenic therapies represents an effective option for tailored and individualized clinical treatments.
Lupu
Mihaela
M
U759 INSERM, Bât.112, Centre Universitaire, Orsay, France. mihaela.lupu@curie.u-psud.fr
Thomas
Carole D
CD
Maillard
Philippe
P
Loock
Bernard
B
Chauvin
Benoit
B
Aerts
Isabelle
I
Croisy
Alain
A
Belloir
Elodie
E
Volk
Andreas
A
Mispelter
Joel
J
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000628:therapy*; D012175:Retinoblastoma / Q000188:drug therapy / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents