Abstract 2057: The development and evaluation of a series of novel in vivo imaging models of AML for the assessment of drug efficacy

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA A major obstacle in anti-cancer drug research is the development and validation of suitable in vivo models to examine compound efficacy. Non-solid tumors present a particular set of challenges for preclinical drug testing as these are much more difficult to measure and often require larger group sizes and satellite groups for study end points. In conventional animal models of haematological diseases such as leukemia, cells are implanted using intravenous injection. This can lead to inconsistent engraftment as cells are not introduced directly into the most receptive environment for growth. Disease burden is measured using either terminal end points, or by fluorescence-activated cell sorting on bone marrow or peripheral blood samples. Neither of these strategies make it practical to identify animals in the early stages of leukemic disease development, limiting the ability to examine therapy in these models. The use of optical imaging presents us with the opportunity to follow disease progression at orthotopic sites, and in the case of non-solid tumors, to monitor systemic disease burden in the same animal over time. Here, building on our previous imaging experience with the SEM model of acute lymphoblastic leukemia (ALL) and the Kasumi-1 model of acute myeloid leukemia (AML), we further describe the development of our optical imaging intrafemoral (i.f.) transplantation models, which implant cells directly into the biological niche of interest, correlating with the environment in which disease develops in patients. Luciferase labelled SKNO-1 and MV4-11 pHR-SLIEW AML cells were injected into the bone marrow cavity of the femur of severely immunocompromised NOG (NOD/Shi-scid/IL-2Rγnull) mice lacking B cells, T cells and Natural Killer (NK) cells via the knee joint. These animals were monitored following initial transplantation, and disease burden quantified longitudinally over several weeks using bioluminescent detection. Once engraftment was shown, animals were given treatment with either vehicle or cytarabine and disease burden measured in each individual animal throughout the duration of the study. The ability to quickly identify engrafted animals, and the predictable development of disease demonstrated allows for early therapeutic intervention, and extension of the treatment window. Efficacy of treatment can be easily followed by optical imaging, and as such, these models provide an attractive, clinically relevant environment for the preclinical assessment of novel therapeutics and combination treatment regimens. Citation Format: Michael A. Batey, Frida Ponthan, Helen J. Blair, Olaf Heidenreich. The development and evaluation of a series of novel in vivo imaging models of AML for the assessment of drug efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2057. doi:10.1158/1538-7445.AM2014-2057