[⁶⁸Ga]NOTA-Galactosyl Human Serum Albumin: a Tracer for Liver Function Imaging with Improved Stability

Non-invasive techniques allowing quantitative determination of the functional liver mass are of great interest for patient management in a variety of clinical settings. Recently, we presented [⁶⁸Ga]DTPA-GSA to target the hepatic asialoglycoprotein receptor for this purpose. Here, we introduce [⁶⁸Ga]NOTA-GSA to improve metabolic stability of the radiopharmaceutical and compare the imaging properties with [⁶⁸Ga]DTPA-GSA.

Labeling of the compounds was carried out at room temperature using 1.9 M sodium acetate as buffer. For quality control, thin-layer, high-performance liquid, and size exclusion chromatographies were used. Metabolic stability was studied in rat and human serums. For in vivo evaluation, Fischer rats were scanned by positron emission tomography and magnetic resonance imaging and subsequently sacrificed for biodistribution studies. Time activity curves (TACs) for heart and liver were generated and corresponding parameters (T₅₀, T₉₀, LHL15, HH15) were calculated.

[⁶⁸Ga]NOTA-GSA can be produced in high radiochemical yield and purity (>95 %) within 15 min. Stability studies revealed almost no metabolite formation over the 2-h observation period. Analysis of the TACs showed comparable results for most of the investigated parameters. The only significant difference was found in the T₉₀ value, where [⁶⁸Ga]NOTA-GSA showed slower uptake in comparison with ⁶⁸Ga-DTPA-GSA (123 ± 10 vs. 89 ± 3 s, p < 0.01).

[⁶⁸Ga]NOTA-GSA showed a significant increase of the metabolic stability and in most organs lower background activity. However, comparison of LHL15 and HH15 indicates that the increased stability did not further improve the diagnostic value. Thus, [⁶⁸Ga]NOTA-GSA and [⁶⁸Ga]DTPA-GSA can be used equivalent for imaging hepatic function with positron emission tomography.