Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach

6533b826fe1ef96bd1283c20

RESEARCH PRODUCT

Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach

Tilmann Grus Frank Rösch Mathias Schreckenberger Hanane Lahnif Stefanie Pektor Lukas Greifenstein

subject

Diagnostic Imaging Glutamate Carboxypeptidase II Biodistribution media_common.quotation_subject Pharmaceutical Science Organic chemistry Chemistry Techniques Synthetic urologic and male genital diseases Article Analytical Chemistry Translational Research Biomedical Mice chemistry.chemical_compound hybrid chelator Nude mouse QD241-441 In vivo Neoplasms Drug Discovery LNCaP Animals Humans Chelation radionuclide diagnosis and therapy Physical and Theoretical Chemistry Internalization Chelating Agents media_common Molecular Structure biology Chemistry Radiochemistry biology.organism_classification Disease Models Animal Kinetics Chemistry (miscellaneous)Isotope Labeling Antigens Surface Heterografts Molecular Medicine Radiopharmaceuticals Ammonium acetate Ex vivo prostate specific membrane antigen PSMA Protein Binding

description

(1) Background: Prostate-specific membrane antigen (PSMA) has been extensively studied in the last decade. It became a promising biological target in the diagnosis and therapy of PSMA-expressing cancer diseases. Although there are several radiolabeled PSMA inhibitors available, the search for new compounds with improved pharmacokinetic properties and simplified synthesis is still ongoing. In this study, we developed PSMA ligands with two different hybrid chelators and a modified linker. Both compounds have displayed a promising pharmacokinetic profile. (2) Methods: DATA5m.SA.KuE and AAZTA5.SA.KuE were synthesized. DATA5m.SA.KuE was labeled with gallium-68 and radiochemical yields of various amounts of precursor at different temperatures were determined. Complex stability in phosphate-buffered saline (PBS) and human serum (HS) was examined at 37 °C. Binding affinity and internalization ratio were determined in in vitro assays using PSMA-positive LNCaP cells. Tumor accumulation and biodistribution were evaluated in vivo and ex vivo using an LNCaP Balb/c nude mouse model. All experiments were conducted with PSMA-11 as reference. (3) Results: DATA5m.SA.KuE was synthesized successfully. AAZTA5.SA.KuE was synthesized and labeled according to the literature. Radiolabeling of DATA5m.SA.KuE with gallium-68 was performed in ammonium acetate buffer (1 M, pH 5.5). High radiochemical yields (&gt

year	journal	country	edition	language
2021-10-20	Molecules

10.3390/molecules26216332 http://europepmc.org/articles/PMC8588462