Nuklearmedizin 2020; 59(02): 218
DOI: 10.1055/s-0040-1708205
Wissenschaftliche Vorträge
Radiochemie und -pharmazie
© Georg Thieme Verlag KG Stuttgart · New York

AAZTA5.SA.KuE, a versatile tool for theranostic application – labeling, in vitro, and first in vivo-investigation of [ 177 Lu]Lu- AAZTA 5 .SA.KuE

L Greifenstein
1   Johannes-Gutenberg University, Institute of Nuclear Chemistry, Mainz
,
T Grus
1   Johannes-Gutenberg University, Institute of Nuclear Chemistry, Mainz
,
D Mathé
2   Semmelweis University, Institute of Biophysics and Radiation Biology, Budapest
,
R Bergmann
2   Semmelweis University, Institute of Biophysics and Radiation Biology, Budapest
,
F Rösch
1   Johannes-Gutenberg University, Institute of Nuclear Chemistry, Mainz
› Author Affiliations
Further Information

Publication History

Publication Date:
08 April 2020 (online)

 

Ziel/Aim The aim of this work was to evaluate the labelling of the PSMA-inhibitor AAZTA5.SA.KuE with 177Lu as well as with 68Ga and 44Sc. Furthermore, its stability should be investigated in vitro and first small animal in vivo studies should be carried out.

Methodik/Methods The chelator AAZTA5 was synthesized in eight steps and conjugated to the KuE (Lysine-urea-glutamate) target vector, using squaric acid as coupling agent in additional two steps. Labeling was performed with gallium-68, scandium-44 and lutetium-177 and radiochemical yields of different amounts of tracer substance were determined using different labeling conditions. In vitro stability in phosphate-buffered saline and human serum was examined at 37 °C and first in vivo SPECT studies were performed with NMRI-Foxn1nu/nu mice with a PC3-PSCA-PSMA tumor.

Ergebnisse/Results AAZTA5.SA.KuE was synthesized with an overall yield of 0.5  % after eleven steps. Radiolabeling of AAZTA5.SA.KuE reached RCY of 95 to 99  % after one minute for labeling with gallium-68 and lutetium-177 at ambient temperature. The labeling with scandium-44 gives a RCY of 89.9 ± 0.3  % after 30 minutes at room temperature. All radiometal-ligand complexes were sufficiently stable in phosphate-buffered saline and human serum over 2 h for gallium-68, 24 h for scandium-44 and 48 h for lutetium-177, respectively. First in vivo-SPECT studies with [177Lu]Lu- AAZTA5.SA.KuE were performed and indicate a good distribution leading to an almost exclusive accumulation of [177Lu]Lu- AAZTA5.SA.KuE in the tumor after 48 h.

Schlussfolgerungen/Conclusions In addition to the simple, mild and versatile labelling of AAZTA5.SA.PSMA, the in vivo application of the 177-lutetium labelled derivative was also investigated and indicated for the first time.