Abstract 20361: Evaluation of AAV9 Delivery and Gene Expression in a Mouse Model of PAD Using the Sodium Iodide Symporter and SPECT/CT

Introduction: Peripheral arterial disease (PAD) is complicated by claudication and amputation. Efforts to stimulate angiogenesis and improve flow with gene therapy have been met with limited success. AAV9 gene delivery can be effective under low flow conditions. Hypothesis: We hypothesize that the sodium iodide symporter (NIS) can be used as a reporter gene to noninvasively track the temporal and spatial distribution of AVV9 gene delivery in PAD model in vivo with SPECT/CT imaging. Methods: Hindlimb ischemia was surgically induced in 12 mice on right leg, and this leg was injected with 2*10^vgp AAV9 of pzac2.1-CMV-NIS-IRES-eGFP (AAV9- CMV-NIS) in the ischemic gastrocnemius (GA) 7 days following surgery. The left, non-ischemic GA was either injected with PBS (n=6) or remained untreated (n=6). In addition, 2*10^vgp of AAV9- CMV-NIS was co-injected with the sialidase, neuraminidase (NM, 0.010 units) in the right GA of 6 mice, while 2*10^vgp of AAV9- CMV-NIS alone was injected into the left GA of these mice. ...