In vivo tracking of 111 In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis Ali Gholamrezanezhad a, ⁎ , Sahar Mirpour a , Mohammad Bagheri b , Mehdi Mohamadnejad b , Kamran Alimoghaddam c , Leila Abdolahzadeh b , Mohsen Saghari a , Reza Malekzadeh b a Research Institute for Nuclear Medicine. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114, Iran b Digestive Disease Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114, Iran c Hematology and BMT Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114, Iran Received 25 January 2011; received in revised form 29 March 2011; accepted 30 March 2011 Abstract Background: Several animal and few human studies suggest the beneficial role of bone marrow mesenchymal stem cells (MSCs) in liver cirrhosis. However, little is known about the fate of MSCs after infusion in cirrhotic patients. We evaluated stem cell biodistribution after peripheral infusion of MSCs in four cirrhotic patients. Methods: After three passages of MSCs, the patients received a total of 250–400×10 6 cells, of which only 50% of the cells were labeled. Specific activities of 0.21–0.67 MBq/10 6 cells were maintained for the injected labeled MSCs. Planar whole-body acquisitions (anterior/ posterior projections) were acquired immediately following infusion as well as at 2 h, 4 h, 6 h, 24 h, 48 h, 7th and 10th days after cell infusion. Results: After intravenous infusion, the radioactivity was first observed to accumulate in the lungs. During the following hours to days, the radioactivity gradually increased in the liver and spleen, with spleen uptake exceeding that in the liver in all patients. Region-of-interest analysis showed that the percentage of cells homing to the liver (following decay and background corrections and geometric mean calculation) increased from 0.0%-2.8% at immediately post-infusion images to 13.0–17.4% in 10th-day post-infusion. Similarly, the residual activities in the spleen increased from 2.0%-10.2% at immediately post-infusion images to 30.1%-42.2% in 10th-day post-infusion. During the same period, the residual activities in the lungs decreased from 27.0–33.5% to 2.0–5.4%. Conclusion: The infusion of MSCs labeled with 111 In-oxine through a peripheral vein is safe in cirrhosis. Cell labeling with 111 In-oxine is a suitable method for tracking MSC distribution after infusion. © 2011 Elsevier Inc. All rights reserved. Keywords: 111 In-oxine; Mesenchymal stem cell; Cirrhosis 1. Introduction Cirrhosis and chronic liver failure are among the most frequent causes of morbidity and mortality throughout the world, with the majority of preventable cases attributed to excessive alcohol consumption, viral hepatitis or nonalco- holic fatty liver disease [1]. Orthotopic liver transplantation is the standard treatment modality in patients with decom- pensated cirrhosis [2]. However, it has several limitations such as shortage of organ donors, high cost, and several complications [2]. Despite progress in medical and surgical treatment, alternative strategies are needed to improve the outcome of patients with cirrhosis. Stem cell therapy may be a potential alternative to liver transplantation. Bone marrow is a reservoir of various stem cells, including hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Several studies have suggested MSC transplantation can reduce liver fibrosis in animal models of cirrhosis [3–6]. Infusion of the cells directly into the vessels feeding the liver (e.g., portal vein or hepatic artery) may improve delivery and subsequent engraftment of the cells into the liver. This method requires an invasive procedure for angiography, and may lead to serious adverse effects, such Available online at www.sciencedirect.com Nuclear Medicine and Biology xx (2011) xxx – xxx www.elsevier.com/locate/nucmedbio ⁎ Corresponding author. E-mail address: agholam1@jhmi.edu (A. Gholamrezanezhad). 0969-8051/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.nucmedbio.2011.03.008