Abstract
PurposeNon-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.ProceduresLabeling 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.Results[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).Conclusions[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.
Highlights
During the last decade, an increasing interest in the use of gallium-68 with positron emission tomography (PET) has Haubner R. et al.: 68Ga-NOTA-galactosyl human serum albumin (GSA) for Liver Function Imaging been observed
To combine the superior performance of PET compared with single-photon emission computed tomography (SPECT) concerning imaging resolution and quantifying properties with the good properties of GSA in asialoglycoprotein receptor (ASGP-R) targeting, we developed a Ga-68-labeled analog [17]. [68Ga]DTPA-GSA showed comparable targeting properties as found for [99mTc]GSA but lack of high metabolic stability
NOTA-GSA was supplied from piCHEM (Graz, Austria) and includes six NOTA, conjugated via isothiocyanate chemistry and 19 galactosyl moieties per human serum albumin (HSA) molecule resulting in an estimated MW of 76,398 g/mol
Summary
An increasing interest in the use of gallium-68 with positron emission tomography (PET) has Haubner R. et al.: 68Ga-NOTA-GSA for Liver Function Imaging been observed. This is mainly based on the improving availability of corresponding Ge-68/Ga-68 generators [1] and due to the very convincing results obtained with Ga-68-labeled radiopharmaceuticals like [68Ga]DOTATOC (see, e.g., [2]) and [68Ga]HBED-PSMA (see, e.g., [3]). [99mTc]diethylenetriamine-pentaacetic acid galactosyl human serum albumin ([99mTc]GSA) [14] binds to the asialoglycoprotein receptor (ASGP-R), a hepatic cell surface receptor specific for galactose terminated glycoproteins [4]. In this study, we introduce with 2-S-(4isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7triacetic acid (p-NCS-Bn-NOTA) an alternative chelating moiety and present stability data as well as the PET imaging properties of [68Ga]NOTA-GSA and compare them with [68Ga]DTPA-GSA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
