How deprotonation changes molecular self-assembly – an AFM study in liquid environment
We study the influence of Alizarin Red S deprotonation on molecular self-assembly at the solid-liquid interface of the natural cleavage plane of calcite immersed in aqueous solution. To elucidate the adsorption details, we perform pH dependent high-resolution atomic force microscopy measurements. When Alizarin Red S is deposited onto calcite(10.4) in a liquid environment at an acidic pH of 5, weakly bound, ordered islands with a (3 x 3) superstructure are observed. A sharp structural transition is revealed when increasing the pH above 8. Above this pH, stable needle-like structures oriented along the [01.0] direction form on the surface. Comparing these results with potentiometric titration…
Development of FAP-inhibitors based on squaric acid linked DOTA and DATA5m chelators
Synthesis, Labeling and Preclinical Evaluation of a Squaric Acid Containing PSMA Inhibitor Labeled with 68 Ga: A Comparison with PSMA‐11 and PSMA‐617
The L-lysine urea-L-glutamate (KuE) represents a key motif in recent diagnostic and therapeutic radiopharmaceuticals targeting the prostate specific membrane antigen (PSMA). Using a squaric acid moiety for coupling of KuE with a radioactive label, the squaric acid as a linker in the PSMA ligand seems to mimic the aromatic structure of the naphthylalanine unit on PSMA-617. In this work, we investigate the influence of squaric acid moiety on the biological activity of the compound carrying a KuE motif and three typical chelates. The derivatives TRAM.SA.KuE, DOTAGA.SA.KuE and NODAGA.SA.KuE were all synthesized in straightforward organic reactions and purified by HPLC afterward. Different amoun…
Squaric Acid-Based Radiopharmaceuticals for Tumor Imaging and Therapy.
Targeting vectors bound to a chelator represent a significant fraction of radiopharmaceuticals used nowadays for diagnostic and therapeutic purposes in nuclear medicine. The use of squaramides as coupling units for chelator and targeting vector helps to circumvent the disadvantages of several common coupling methods. This review gives an overview of the use of squaric acid diesters (SADE) as linking agents. It focuses on the conjugation of cyclic chelators, e.g., DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), as well as hybrid chelators like AAZTA5 (6-pentanoic acid-6-amino-1,4-diazepine tetracetic acid) or DATA5m (6-pentanoic acid-6-amino-1,4-diazapine-triacetate) to diff…
Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach
(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…
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
Mild and efficient 64Cu labeling of perhydro-1, 4-diazepine derivatives for potential use with large peptides, proteins and antibodies
Abstract DATA (6-Amino-1,4-diazapine-triacetate) and AAZTA (6-Amino-1,4-diazapine-tetracetate) chelators represent a novel approach representing hybrid-chelates: possessing significant cyclic and acyclic character. It is believed that flexibility of the acyclic part facilitates rapid complexation, whilst the preorganized cyclic part minimizes the energy barrier to complexation and inhibits decomplexation processes. So far, these chelators have been used exclusively with 44Sc and 68Ga only. Recent results with natCu predict high stabilities for Cu-AAZTA, yet no radioactive labeling of AAZTA or DATA with 64Cu or any additional radioactive isotope has been reported. We present the one pot synt…
Targeting fibroblast activation protein (FAP): next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA5m chelators
Abstract Background Fibroblast activation protein (FAP) is a proline selective serine protease that is overexpressed in tumor stroma and in lesions of many other diseases that are characterized by tissue remodeling. In 2014, a most potent FAP-inhibitor (referred to as UAMC1110) with low nanomolar FAP-affinity and high selectivity toward related enzymes such as prolyl oligopeptidase (PREP) and the dipeptidyl-peptidases (DPPs): DPP4, DPP8/9 and DPP2 were developed. This inhibitor has been adopted recently by other groups to create radiopharmaceuticals by coupling bifunctional chelator-linker systems. Here, we report squaric acid containing bifunctional DATA5m and DOTA chelators relied on UAMC…