[68Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis

This study was designed to determine safety, tolerability, and radiation burden of a [Ga-68]NODAGA-RGD-PET for imaging integrin alpha(v)beta(3) expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled. After injection of 154-184 MBq [Ga-68]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 +/- 2.1, 36.9 +/- 2.8, and 75.1 +/- 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose. The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [Ga-68]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 +/- 0.43, 0.54 +/- 0.39, 0.22 +/- 0.05, and 0.16 +/- 0.8, respectively). The calculated effective dose was 21.5 +/- 5.4 mu Sv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 +/- 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue. [Ga-68]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [Ga-68]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [Ga-68]NODAGA-RGD PET for non-invasive determination of integrin alpha(v)beta(3) expression.