Abstract 2713: Elucidation of bone metastasis using a caudal artery injection mouse model and Akaluc-AkaLumine near-infrared bioluminescence technology

Abstract

Abstract Bone is one of the most common sites of metastasis for various primary tumors including breast, prostate and lung cancers. We have addressed molecular basis underlying bone metastasis using newly developed murine model of bone metastasis and near-infrared bioluminescence technologies. Our new murine model overcomes several limitations in the current standard model by intra-cardiac (IC) injection of cancer cells [1]. We found that the caudal artery is a new pathway to predominantly deliver cancer cells to the bone marrow of hind limbs in mice. Intra-caudal arterial (CA) injection is technically as easy as tail vein injection [2]. In addition, CA injection delivered cancer cells >10-fold more efficiently than IC injection. This accelerated the development of bone metastasis in hind limbs with wide variety of cell lines. We have combined the CA injection model with near-infrared bioluminescence imaging. Bioluminescence imaging (BLI) with firefly luciferases and its natural substrate D-luciferin has been indispensable to noninvasively monitor metastasis development in mice. To improve deep-tissue imaging, synthetic luciferin AkaLumine has successfully extended the wavelength of firefly bioluminescence to the near-infrared region where tissue is more transparent to light [3]. More recently, our collaborators created an engineered luciferase Akaluc that displays high catalytic activity in reaction with AkaLumine [4]. AkaLumine-Akaluc bioluminescence imaging (AkaBLI) is capable of noninvasive visualization of single cancer cells deep inside mice. Combining the CA injection model with AkaBLI technology is a powerful tool for elucidating the mechanism of bone metastasis in small animals.