Artikel
Assessment of the early treatment effects of locally delivered temozolomide by PET and MR imaging in experimental glioblastoma
Suche in Medline nach
Autoren
Veröffentlicht: | 8. Juni 2016 |
---|
Gliederung
Text
Objective: The interstitial delivery of therapeutics to the CNS for glioma therapy is a promising principle but the visualization of early treatment effects remains challenging. This study aimed (i) to assess the efficacy of locally delivered, dissolved temozolomide in an orthotopically implanted glioma model, to (ii) visualize early treatment changes using magnetic resonance (MR) imaging and positron emission tomography (PET) and (iii) to compare the PET tracers 3’-deoxy-3’-[18F]flourothymidine ([18F]FLT) and O-(2-[(18)F]Fluoroethyl)- L-tyrosine (FET) regarding their value for metabolic information in this model.
Method: 48 female athymic nude rats (RNU) were stereotactically implanted with U87 glioma cells. Tumor engraftment was determined by 7Tesla MRI. Local treatment with a single intratumoral stereotactic injection of different concentrations of soluble TMZ was performed on day 15 post implantation. As a control, systemic intraperitoneal treatment was performed on two consecutive days. Growth characteristics and metabolic information were assessed by MRI and PET. In a following survival analysis of the local (n=10, 0.05mg TMZ) and systemic (n=10, 3.75mg TMZ) treatment group compared to an untreated control group (n=10) was obtained.
Results: MRI verified a tumor take rate of 98%. Baseline tumor size (MRI) was similar in all groups. Local therapy with TMZ was feasible but due to therapeutic intratumoral fluid injection, the value of MRI volumetry was limited. FLT- and FET-PET imaging (n=18) was superior to MRI and both tracers were very suitable for the monitoring of the treatment effects based on a distinct tumor-to normal tissue radiotracer uptake. In both treatment groups, proliferation rate was smaller day 7 after therapy and showed only a slight increase compared to the control group within 14 days after therapy. In the Kaplan Meier survival analysis, locally treated rats with survived significantly longer than systemically treated or untreated controls. The locally delivered dose of TMZ was significantly smaller compared to systemic dose and no systemic toxicity was observed.
Conclusions: Local treatment with dissolved TMZ is feasible and showed a significantly longer survival in our model. FLT- and FET- PET imaging offers distinct and reliable assessment of early treatment effects after local delivery of TMZ.