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International audience; PURPOSE: 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 6days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring (188)Re elimination in faeces and urine over 72h 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 72h. Rat median survival was significantly improved for the group treated with 8Gy (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 8Gy proved to be a very effective dose, between toxic (10-12Gy) and ineffective (3-4Gy) 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.

International audience; OBJECTIVE: We report preliminary results from use of a radioreceptor assay (RRA) to measure serum haloperidol levels and their relation to clinical response and adverse effects in 19 psychotic patients with positive symptoms treated with haloperidol. METHODS: Blood samples were taken on Days 7, 14 and 21. Clinical evaluation was based on the PANSS, and UKU scales. The D2 antidopaminergic RRA was used to measure haloperidol serum levels. RESULTS: Our results show a correlation between psychosis with positive symptoms assessed by positive scores in the PANSS and the serum drug level measured by RRA concentrations. The observed relationship made it possible to establish a therapeutic serum range of haloperidol equivalents 15-30 ng/ml-1. This range contained no "non-responders". Analysis of the correlation between each item on the positive subscale of the PANSS and the RRA concentration suggested that there was no specific symptom of psychosis closely related to RRA concentration during the first 15 days of treatment. In the third week, however, certain specific symptoms were closely connected to the RRA concentration. CONCLUSION: From these results, it can be concluded that antipsychotic activity can be related to blockade of serum D2 dopamine receptors. In future would be desirable to monitor neuroleptic treatment in this way. The study also showed that the antipsychotic treatment did not correct any specific component of the psychosis during the first stage of the treatment but that it did so at later times.