Automatic Production and Preclinical Evaluation of 11C-labeled Thiolactic Acid for Cancer Imaging

Introduction: Lactic acid has attracted growing attention and research, particularly in the diagnosis and treatment of tumors as a byproduct of anaerobic glycolysis. In the past, lactic acid was considered a metabolic waste produced during glycolysis under anaerobic conditions. Now it has been proved that lactate plays a direct role in tumor energy metabolism as a significant source of carbon skeleton and as a precursor for gluconeogenesis, especially in regulating cancer progression via multiple mechanisms such as cell cycle regulation, immune suppression, energy metabolism and so on. Meanwhile, lactate is a signaling molecule with autocrine, paracrine, and endocrine effects. As an analogue of lactic acid, thiolactic acid is labeled with [¹¹C]-methyl iodide for tumor imaging studies and evaluated its potential for clinical application in this study.

Methods: Thiolactic acid was labeled with ¹¹C through [11C]methylation using [¹¹C]-methyl iodide and then purified by Sep-pak 18 cartridge. PET imaging and ex vivo biodistribution were assayed to investigate the in vivo performance of xenograft tumor mouse models and glioma orthotopic tumor mouse models. Dynamic PET/CT scaning was conducted on three healthy monkeys to evaluate the biodistribution and metabolic characteristics in normal tissues.

Results: Synthesis of 3-([¹¹C]-methylthio)-lactic acid achieved high radiochemical yield and purity. Small animal PET/CT dynamic imaging showed that 3-([¹¹C]-methylthio)-lactic acid exhibited early and high uptake in the tumor and had a high tumor-to-muscle uptake ratio. The PET/CT image of the healthy monkeys showed that 3-([¹¹C]-methylthio)-lactic acid was mainly metabolized by the liver and excreted through the urinary system. There was a relatively low uptake and rapid clearance of radioactivity in other organs such as the stomach, spleen, lung, heart, brain, muscles, and intestines.

Conclusions: The 3-([¹¹C]-methylthio)-lactic acid can be prepared rapid and efficient via automation and the biological evaluations indicate that 3-([¹¹C]-methylthio)-lactic acid might be a potential PET tracer for tumor imaging.