TY - JOUR T1 - Quantitative MRI Establishes the Efficacy of PI3K Inhibitor (GDC-0941) Multi-Treatments in PTEN-deficient Mice Lymphoma JF - Anticancer Research JO - Anticancer Res SP - 415 LP - 420 VL - 32 IS - 2 AU - STEPHAN WULLSCHLEGER AU - JUAN M. GARCÍA-MARTÍNEZ AU - SUZANNE L. DUCE Y1 - 2012/02/01 UR - http://ar.iiarjournals.org/content/32/2/415.abstract N2 - Aim: To assess the efficacy of multiple treatment of phosphatidylinositol-3-kinase (PI3K) inhibitor on autochthonous tumours in phosphatase and tensin homologue (Pten)-deficient genetically engineered mouse cancer models using a longitudinal magnetic resonance imaging (MRI) protocol. Materials and Methods: Using 3D MRI, B-cell follicular lymphoma growth was quantified in a Pten+/−Lkb1+/hypo mouse line, before, during and after repeated treatments with a PI3K inhibitor GDC-0941 (75 mg/kg). Results: Mean pre-treatment linear tumour growth rate was 16.5±12.8 mm3/week. Repeated 28-day GDC-0941 administration, with 21 days ‘off-treatment’, induced average tumour regression of 41±7%. Upon cessation of the second treatment (which was not permanently cytocidal), tumours re-grew with an average linear growth rate of 40.1±15.5 mm3/week. There was no evidence of chemoresistance. Conclusion: This protocol can accommodate complex dosing schedules, as well as combine different cancer therapies. It reduces biological variability problems and resulted in a 10-fold reduction in mouse numbers compared with terminal assessment methods. It is ideal for preclinical efficacy studies and for phenotyping molecularly characterized mouse models when investigating gene function. ER -