188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas.
OBJECTIVE
Lipid nanocapsules (LNC) entrapping lipophilic complexes of (188)Re ((188)Re(S(3)CPh)(2)(S(2)CPh) [(188)Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of (188)Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model.


METHODS
Female Fischer rats with 9L glioma were treated with a single injection of (188)Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3 Gy in comparison with blank LNC, perrhenate solution (4 Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring (188)Re elimination in faeces and urine over 72 h after the CED injection. The therapeutic effect of (188)Re-SSS LNC was assessed based on animal survival.


RESULTS
CED of (188)Re perrhenate solution resulted in rapid drug clearance with a brain T (1/2) of 7h. In contrast, when administered in LNC, (188)Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72 h. Rat median survival was significantly improved for the group treated with 8 Gy (188)Re-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8 Gy proved to be a very effective dose, between toxic (10-12 Gy) and ineffective (3-4 Gy) doses.


CONCLUSIONS
These findings show that CED of (188)Re-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of (188)Re internal radiotherapy for the treatment of brain malignancy.
Allard
E
E
INSERM U646, Université d'Angers, Angers 49100, France.
Hindre
F
F
Passirani
C
C
Lemaire
L
L
Lepareur
N
N
Noiret
N
N
Menei
P
P
Benoit
J-P
JP
D000818:Animals; D001426:Bacterial Proteins; D001932:Brain Neoplasms / Q000175:diagnosis / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D018316:Gliosarcoma / Q000175:diagnosis / Q000532:radiotherapy*; D005964:Glucosyltransferases; D008055:Lipids / Q000737:chemistry*; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D012211:Rhenium / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
D001426:Bacterial Proteins; D004337:Drug Carriers; D008055:Lipids; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D005964:Glucosyltransferases; C430878:Tts protein, Streptococcus pneumoniae