Radiolabeled L-lysine for tumor imaging.

Rationale and Objectives: The aims of this study were to label the versatile amino acid l-lysine with ^99mTc using 2,3-dimercapto-succinic acid (DMSA) as a chelator, and to assess its tumor imaging feasibility under in vivo and in vitro conditions, and finally to determine the subcellular biodistribution of this radiopharmaceutical. Materials and Methods: DMSA-l-lysine was chemically synthesized and labeled with sodium pertechnetate. Nuclear magnetic resonance (NMR) and mass spectral analysis of DMSA-l-lysine were conducted. Radiochemical purity was determined by thin-layer chromatography (TLC) and paper chromatography. Cellular uptake, competition and subcellular localization studies were performed in rat breast cancer cells (13762). In vivo studies of planar imaging and biodistribution studies were performed on female Fischer 344 rats. Medical Internal Radiation Dose (MIRD) dosimetry estimates were calculated. Results: Radiochemical purity (determined by radio-TLC and high-performance liquid chromatography) of these compounds was >95%. ^99mTc-DMSA-l-lysine showed good uptake in in vitro cell culture assays and uptake was reduced in competition studies. ^99mTc-DMSA-l-lysine accumulates in the nucleus as much as in the cytoplasm and it was also shown that accumulation of the ^99mTc-DMSA-l-lysine in the nucleus increases as a function of a time. There was an increase in tumor-to-blood and tumor-to-muscle count density ratios. Tumor/background ratios were 5.75 at 1 hour and 6.87 at 2 hours. In vivo tissue distribution studies revealed that radiation dosimetry of blood-forming organs were within radiation dose limits. Conclusion: DMSA-l-lysine kits can be labeled with ^99mTc easily and efficiently, with high radiochemical purity and cost-effectiveness. In vitro cellular uptake and scintigraphic imaging studies demonstrated the pharmacokinetic distribution and feasibility of using ^99mTc-DMSA-l-lysine for tumor imaging. [Copyright &y& Elsevier]