Ga-68-labeled neolactosylated human serum albumin (LSA) for PET imaging of hepatic asialoglycoprotein receptor

Abstract Introduction The purpose of this study was the development of 68 Ga-labeled neolactosylated human serum albumin (LSA) for imaging asialoglycoprotein receptors in the liver by using positron emission tomography (PET), which would enable functional imaging with higher resolution than single-photon emission computed tomography (SPECT). Methods LSA was synthesized by conjugating α-lactose to human serum albumin (HSA) by reductive amination. LSA was conjugated with 2-( p -isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-NOTA) and the resultant NOTA-LSA was labeled with 68 Ga at room temperature. The labeling efficiency of NOTA-LSA was evaluated as a function of pH and time. The stability of 68 Ga-NOTA-LSA in phosphate buffered saline (PBS) and human serum at 37 °C was determined. Biodistribution and PET studies of 68 Ga-NOTA-LSA were performed in mice following tail vein injection of radiotracer. Results The numbers of lactose and NOTA units per HSA were determined to be 31.7 and 4.6, respectively. When the reaction was done at room temperature, the labeling efficiency of NOTA-LSA was higher than 99% at pH 4.8 and 96% at pH 6. More than 95% of the detected radioactivity was associated with the intact molecule for at least the 4 h following synthesis when incubated in PBS or human serum at 37 °C. Biodistribution and animal PET studies showed specific retention of 68 Ga-NOTA-LSA in liver following intravenous administration. Conclusion 68 Ga-NOTA-LSA was successfully developed for imaging asialoglycoprotein receptors in the liver with a simple labeling method, high labeling efficiency, and high stability.