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

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 4h 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.