A recently established model in which glioblastoma biopsybased spheroids are serially passaged in the brains of nude rats shows highly invasive and angiogenic features [3] . Therefore, this model is well suited for the study of new therapeutic strategies. Still, reports using this or other clinically relevant models for experimental therapy are scarce. Recently, we analyzed the therapeutic potential of the HSV-1-based oncolytic Herpes vector G207 in the biopsy spheroid-based GBM model. The tumor volume in treated animals was reduced compared to control groups, but there was no significant survival advantage [4] . In contrast, the same therapy was more effective in a cell line-based animal model [5] and as a result is currently investigated in a phase I/II clinical study [6] . In the present investigation we used the invasive xenograft model to evaluate transduction and therapeutic efficacy of lentiviral pseudotyped vectors. Gammaretroviral vectors derived from the Moloney murine leukemia virus (MMLV) have been the most frequently used retroviruses for gene therapy of brain tumors [7] [8] [9] [10] . However, despite promising results in animal models, clinical trials using retroviral vector supernatants or retroviral packaging cells have failed [11] [12] [13] . One major drawback of gammaretroviral vectors is the exclusive transduction of dividing cells, since in human gliomas, the majority of tumor cells do not divide within a given treatment window. Therefore, lentiviral vectors with their ability to also transduce non-dividing cells are attractive candidates for the treatment of brain cancer. In previous studies, we have developed gammaretroviral and lentiviral vectors pseudotyped with the glycoproteins (GP) of the lymphocytic choriomeningitis virus (LCMV) [14, 15] . These vectors have a broad host range and can be concentrated by ultracentrifugation for in vivo applications. In addition, LCMV-GP is not cytotoxic, and stable recombinant packaging cell lines can be established [16, 17] . Recently, we showed that lentiviral LCMV-GP pseudotypes efficiently delivered transgenes to rat glioma cells in vivo, while resident neurons were not transduced [18] . Furthermore, we showed a significant therapeutic effect of LCMV-GP pseudotyped lentiviral vectors in the cell-line based 9L rat glioma model using the suicide gene HSV-1-tk. VSV-G lentiviral pseudotypes also showed a significant efficacy, similar to that of LCMV pseudotypes, which was mainly mediated by a bystander effect of transduced normal brain cells [19] .