Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first¹⁸F-labeled cyclic RGD peptide as radiotracer for imaging integrinαvβ3expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, includingα5β1andαvβ6, came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [¹⁸F]Galacto-RGD. This includes recently developed¹⁸F-labeling strategies and also new approaches in⁶⁸Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrinα5β1andαvβ6will be summarized and discussed.

Purpose This study was designed to determine safety, tolerability, and radiation burden of a [⁶⁸Ga]NODAGA-RGD-PET for imaging integrin α_vβ₃ expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled. Methods After injection of 154–184 MBq [⁶⁸Ga]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. Results 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.). [⁶⁸Ga]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 μSv/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. Conclusions [⁶⁸Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [⁶⁸Ga]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 [⁶⁸Ga]NODAGA-RGD PET for non-invasive determination of integrin α_vβ₃ expression.