RT Journal Article SR Electronic T1 Non-invasive imaging of drug-induced liver injury with 18F-DFA PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.117.206961 DO 10.2967/jnumed.117.206961 A1 Salas, Jessica R. A1 Chen, Bao Ying A1 Wong, Alicia A1 Duarte, Sergio A1 Angarita, Stephanie A. K. A1 Lipshutz, Gerald S. A1 Witte, Owen N. A1 Clark, Peter M. YR 2018 UL http://jnm.snmjournals.org/content/early/2018/02/28/jnumed.117.206961.abstract AB Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed. Methods: We evaluate in a preclinical model whether 18F-2-deoxy-2-fluoroarabinose (18F-DFA), a PET radiotracer that measures the ribose salvage pathway, can be used to monitor acetaminophen-induced liver injury and failure. Mice treated with vehicle, 100, 300, or 500 mg/kg acetaminophen for 7 or 21 hours were imaged with 18F-FDG and 18F-DFA PET. Hepatic radiotracer accumulation was correlated to survival and percent of non-necrotic tissue in the liver. Mice treated with acetaminophen and vehicle or N-acetylcysteine were imaged with 18F-DFA PET. 18F-DFA accumulation was evaluated in human hepatocytes engrafted into the mouse liver. Results: We show that hepatic 18F-DFA accumulation is 49 - 52% lower in mice treated with high dose acetaminophen than in mice treated with low or no dose acetaminophen. Under these same conditions, hepatic 18F-FDG accumulation was unaffected. At 21 hours post-acetaminophen treatment, hepatic 18F-DFA accumulation can distinguish mice that will succumb to the liver injury from those that will survive it (6.2 versus 9.7 signal/background, respectively). Hepatic 18F-DFA accumulation in this model provides a tomographic representation of hepatocyte density in the liver, with a R2 between hepatic 18F-DFA accumulation and percent non-necrotic tissue of 0.70. PET imaging with 18F-DFA can be used to distinguish effective from ineffective resolution of acetaminophen-induced liver injury with N-acetylcysteine (15.6 versus 6.2 signal/background, respectively). Human hepatocytes, in culture or engrafted into a mouse liver, have similar levels of ribose salvage activity to mouse hepatocytes. Conclusion: Our findings suggest that PET imaging with 18F-DFA can be used to visualize and quantify drug-induced acute liver injury and may provide information on the progression from liver injury to hepatic failure.