Photodynamic therapy using motexafin lutetium in allograft coronary artery disease

Graft coronary artery disease (GCAD) limits long-term patient survival following heart transplantation. There are few treatment options. Exploration into less invasive diagnostic techniques and attenuation of allograft coronary disease is warranted. The selectivity of Antrin^® Injection (a motexafin lutetium sensitizer, Lu-Tex) and illumination with far-red light, approximately 732 nm, has been evaluated in several preclinical atherosclerosis models. Lu-Tex, using fluorescence microscopy, was found to partition into distinct punctate cytoplasmic compartments in cultured human bypass coronary smooth muscle cells (SMCs). Using specific organelle probes the chief subcellular localization sites were lysosomes and endoplasmic reticulum. The inhibitory effect of Lu-Tex-mediated photoactivation was demonstrated using SMCs; many cells died via an apoptotic pathway. Following illumination, fluorescence microscopy revealed sensitizer redistribution with fluorescence being observed in the mitochondria. The distribution of Lu-Tex was evaluated in a rat model of heterotopic cardiac allografts 60 days after transplantation. Lu-Tex was retained in the cardiac allograft, exhibiting a five-fold increase in retention between the allograft and native heart. These results encourage further exploration of Lu-Tex for diagnosis, and possible amelioration of chronic graft vascular disease using photodynamic therapy.