Development of 68Ga-labelled DTPA galactosyl human serum albumin for liver function imaging

The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [99mTc]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([99mTc]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [68Ga]GSA for the potential use with positron emission tomography (PET). Labelling of GSA with 68Ga was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [68Ga]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [68Ga]GSA distribution in Lewis rats was compared with [99mTc]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [68Ga]GSA and [99mTc]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90). [68Ga]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free 68Ga include 0.1 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 [68Ga]GSA compared to [99mTc]GSA. The [99mTc]GSA TACs exhibited a small degree of hepatic metabolism compared to the [68Ga]GSA curves. The mean [68Ga]GSA t90 was higher than the mean t90 for [99mTc]GSA. The mean [68Ga]GSA t50 was not significantly different from the mean t50 for [99mTc]GSA. This study provides a promising new 68Ga-labelled compound based on a commercially used kit for imaging the functional hepatocellular mass. (orig.)