Authors: Roland Haubner David R Vera Salman FarshchiHeydari Anna Helbok Christine Rangger Daniel Putzer Irene J Virgolini
Publish Date: 2013/04/12
Volume: 40, Issue: 8, Pages: 1245-1255
Abstract
The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptormediated endocytosis It has been shown that imaging of the receptor density using 99mTcdiethylenetriamine pentaacetic acid DTPA galactosyl human serum albumin 99mTcGSA allows noninvasive determination of functional hepatocellular mass Here we present the synthesis and evaluation of 68GaGSA for the potential use with positron emission tomography PETLabelling of GSA with 68Ga was carried out using a fractionated elution protocol For quality control thinlayer chromatography TLC highperformance liquid chromatography HPLC and size exclusion chromatography SEC techniques were evaluated Stability of 68GaGSA was studied in phosphatebuffered saline PBS and human serum For in vivo evaluation 68GaGSA distribution in Lewis rats was compared with 99mTcGSA by using a dual isotope protocol PET and planar imaging studies were performed using the same scaled molar dose of 68GaGSA and 99mTcGSA Timeactivity curves TAC for heart and liver were generated and corresponding parameters calculated t50 t9068GaGSA can be produced with high radiochemical purity The best TLC methods for determining potential free 68Ga include 01 M sodium citrate as eluent None of the TLC methods tested were able to determine potential colloids This can be achieved by SEC HPLC confirmed high radiochemical purity 98 Stability after 120 min incubation at 37 °C was high in PBS 95 intact tracer and low in human serum ∼27 intact tracer Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake whereas activity concentration in blood was higher for 68GaGSA compared to 99mTcGSA The 99mTcGSA TACs exhibited a small degree of hepatic metabolism compared to the 68GaGSA curves The mean 68GaGSA t90 was higher than the mean t90 for 99mTcGSA The mean 68GaGSA t50 was not significantly different from the mean t50 for 99mTcGSA
Keywords: