Evaluation of Protic Ionic Liquids Based on Triethanolammonium and Tris(hydroxymethyl)methylammonium Salts as Buffers for ⁶⁸Ga‐Radiolabelling of PSMA‐HBED‐CC

Abstract

Nowadays chemistry of 68Ga‐labelled radiopharmaceuticals is one of the drivers for Positron Emission Tomography (PET). Buffers solutions for radiolabelling play one of the important roles here. Despite HEPES buffer providing high radiochemical conversions, its use is undesirable due to high toxicity. In this article we report a simple procedure involving usage of aqueous triethanolammonium (TEA) and tris(hydroxymethyl)methyl‐ammonium (TRIS) salts of biologically active carboxylic acids in a process of gallium‐68 complexation with PSMA‐HBED‐CC. These salts provide not only high radiochemical conversions but also are already widely used in biochemistry, molecular biology, agriculture and medicine as drugs of a wide spectrum of action and growth stimulating drugs (Trekrezan™, Chlorokrezacin™).

Radiolabeling Strategies of Micron- and Submicron-Sized Core–Shell Carriers for In Vivo Studies

“…It is worth noting that radiolabeling efficiency strongly depends on the used buffer solution where the reaction takes place . The HEPES buffer has attracted the most significant attention among Good’s buffers used for radiolabeling. − However, in this study, triethanolammonium benzoate (TEA benzoate) was employed for the conjugation of 68 Ga with DOTA because of its decreased toxicity compared to HEPES buffer. , Moreover, previous studies demonstrated the high efficiency of 68 Ga radiolabeling in TEA benzoate buffer compared to the HEPES buffer due to the unique atrane structure characterized by a tricyclic endo-conformation closed by three intramolecular hydrogen bonds HO···H N . − …”

Contribution of the Scientific School of Academician M.G. Voronkov to the Development of the Chemistry of Biologically Active Atranes (Protatranes and Hydrometallatranes) (A Review)

“…Joint research with Granov Russian Scientific Center of Radiology and Surgical Technologies [ 95 , 96 ] have shown that the synthesized hydroxyalkylammonium carboxylates are promising buffering agents for the preparation of gallium-68 complexes with chelators and peptides. The 68 Ga complexes with a series of clinically important peptides are radiopharmaceuticals important in the nuclear medicine for the diagnostics of various neoplasms.…”

Alkanolammonium Protic Ionic Liquids for Low Temperature 68Ga‐Radiolabeling of DOTA‐Functionalized Compounds

“…Recently we reported that TEA and TRIS salts of carboxylic acids are a perspective alternative to toxic HEPES buffer and can be used as buffers for 68 Ga-radiolabeling of PSMA-HBED-CC (PSMA-11), peptide with acyclic chelator used in PET diagnosis of prostate cancer. [9] The main goal of this work was to investigate the dependence of different factors (temperature of labeling, amount of peptide, nature of buffer, and addition of organic solvents) on the formation of the 68 Ga complex with p-SCN-Bn-DOTA chelator and clinically relevant peptides DOTA-NOC and DOTA-TATE.…”

“…Alkanolammonium buffers, namely TEA, TRIS, and PDA salts of carboxylic acids, were used as buffer agents in this experiment. Based on previously obtained data, [9] we selected benzoic (Benz), cinnamic (Cin), salicylic (Sal), acetylsalicylic (AcSal), 2-methylphenoxyacetic (Crez), 4-chloro-2-methylphenoxyacetic (ClCrez) and succinic (HSuc -hydrosuccinate and Suc -succinate) acids as anions for the synthesis of TEA, TRIS, and PDA salts. PDA salts ( Figure 1) were firstly synthesized by the reaction of PDA with the corresponding carboxylic acid in MeOH and yielded as solid powders or viscous oils.…”

“…The radiolabeling was performed according to our previously published method. [9] Briefly, 68 Ga 3 + in 0.1 M HCl (0.5 ml) was mixed with 10 μg of p-SCN-Bn-DOTA, 100 μL of 1 M alkanolammonium buffer solution in water and 150 μL of EtOH (for PDA salts 250 μL of 0.4 M solution in water/EtOH = 1 : 1.5) in a 2 ml microcentrifuge tube. The mixture was vortexed and incubated at 95°C for 10 min.…”