Automation of (64)Cu production at Turku PET Centre.

At Turku PET Centre automation for handling solid targets for the production of (64)Cu has been built. The system consists of a module for moving the target from the irradiation position into a lead transport shield and a robotic-arm assisted setup for moving the target within radiochemistry laboratory. The main motivation for designing automation arises from radiation hygiene.

64Cu- and 68Ga-labelled [Nle(14),Lys(40)(Ahx-NODAGA)NH2]-exendin-4 for pancreatic beta cell imaging in rats.

PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx-NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx-NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. PROCEDURES: The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. RESULTS: We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. CONCLUSION: [(64)Cu]NODAGA-exendin-4 might be more effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [(64)Cu]NODAGA-exendin-4 as a clinical tracer.

Synthesis and preclinical characterization of [64Cu]NODAGA-MAL-exendin-4 with a Nε-maleoyl-L-lysyl-glycine linkage.

INTRODUCTION: Renal localization of high radioactivity levels during targeted imaging compromises tissue visualization in the kidney region and limits diagnostic accuracy. Radioiodinated antibody fragments with a renal enzyme-cleavable N(ε)-maleoyl-L-lysyl-glycine (MAL) linkage demonstrated low renal radioactivity levels in mice, from early postinjection times. This study tested the hypothesis whether a (64)Cu-labeled NODAGA-exendin-4 peptide with a MAL linkage ([(64)Cu]NODAGA-MAL-exendin-4) could decrease kidney radioactivity levels in rats, compared to a [(64)Cu]NODAGA-exendin-4 reference, without impairing the radioactivity levels in the target tissue. METHODS: NODAGA-MAL-exendin-4 was synthesized in a two-phase approach using solid support to prepare maleoyl-derivatized NODAGA followed by Michael addition to cysteine-derivatized exendin-4 in solution. Radiolabeling was performed in buffered aqua with [(64)Cu]CuCl2, which was produced via the (64)Ni(p,n)(64)Cu nuclear reaction. The in vitro and in vivo stability, lipophilicity, and distribution kinetics in major rat organs for [(64)Cu]NODAGA-MAL-exendin-4 were studied and compared to [(64)Cu]NODAGA-exendin-4. Labeling of pancreatic islets was assessed using autoradiography. RESULTS: NODAGA-MAL-exendin-4 was synthesized, with an overall yield of 9%, and radiolabeled with (64)Cu with high specific radioactivity. Serum incubation studies showed high stability for [(64)Cu]NODAGA-MAL-exendin-4. Similar tissue distribution kinetics was observed for [(64)Cu]NODAGA-MAL-exendin-4 and [(64)Cu]NODAGA-exendin-4, with high kidney radioactivity levels. CONCLUSIONS: The incorporated MAL linkage in [(64)Cu]NODAGA-MAL-exendin-4 was unable to reduce kidney radioactivity levels, compared to [(64)Cu]NODAGA-exendin-4. The applicability of metabolizable linkages in the design of kidney-saving exendin-4 analogs requires further investigation.