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

• Published in: Molecular imaging and biology 2017-10, Vol.19 (5), p.723-730
• Main Authors: Haubner, Roland, Schmid, Andreas M., Maurer, Andreas, Rangger, Christine, Roig, Llanos Geraldo, Pichler, Bernd J., Virgolini, Irene J.
• Format: Article
• Language: English
• Subjects: Acetic acid; Albumin; Animals; Control stability; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Diagnostic systems; Emission analysis; Gadolinium - chemistry; Human serum albumin; Humans; Imaging; Liver; Liver - physiology; Liver Function Tests; Magnetic resonance imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Metabolism; Metabolites; Molecular Imaging - methods; Organs; Pentetic Acid - chemistry; Pharmaceuticals; Positron emission; Positron emission tomography; Quality control; Radiochemical analysis; Radioisotopes; Radiology; Rats; Rats, Inbred F344; Research Article; Serum albumin; Serum Albumin, Human - chemistry; Sodium; Sodium acetate; Stability analysis; Tissue Distribution; Tomography
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-017-1046-1

Purpose 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 [ 68 Ga]DTPA-GSA to target the hepatic asialoglycoprotein receptor for this purpose. Here, we introduce [ 68 Ga]NOTA-GSA to improve metabolic stability of the radiopharmaceutical and compare the imaging properties with [ 68 Ga]DTPA-GSA. Procedures 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 (T 50 , T 90 , LHL15, HH15) were calculated. Results [ 68 Ga]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 T 90 value, where [ 68 Ga]NOTA-GSA showed slower uptake in comparison with 68 Ga-DTPA-GSA (123 ± 10 vs. 89 ± 3 s, p