Synthesis and evaluation of a para-carboxylated benzyl-DOTA for labeling peptides and polypeptides

Suzuki, Hiroyuki; Ichinohe, Kento; Araki, Mari; Muramatsu, Sayumi; Uehara, Tomoya; Arano, Yasushi

doi:10.1016/j.nucmedbio.2022.08.003

Cited by 2 publications

(12 citation statements)

References 30 publications

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“…DOTA-Bn-TOC and DOTATOC were prepared from the same procedure described previously. 29 The syntheses of DOTAGAM Bu , DO3AM Bu , and p -NO 2 -Bn-DO3A are described in the Supporting Information . The other chemicals obtained from the commercial sources were of reagent grade or higher and were used without further purification.…”

Section: Methodsmentioning

confidence: 99%

“…p -NO 2 -Bn-DOTA and DOTA were purchased from Macrocyclics (Texas, USA) and Tokyo Chemical Industry (Tokyo, Japan), respectively. DOTA-Bn-TOC and DOTATOC were prepared from the same procedure described previously . The syntheses of DOTAGAM Bu , DO3AM Bu , and p -NO 2 -Bn-DO3A are described in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the stability of [ 67 Ga]Ga-Bn-DOTA was further assessed after conjugation to a peptide using a newly developed bifunctional Bn-DOTA, p -COOH-Bn-DOTA( t Bu) 4 . Its applicability to the solid-phase peptide synthesis was confirmed by synthesizing the p -COOH-Bn-DOTA-conjugated [Tyr 3 ]octreotide (TOC) analogue, DOTA-Bn-TOC (Figure A) . The stability of [ 67 Ga]Ga-DOTA-Bn-TOC (Figure A) was compared with [ 67 Ga]Ga-DOTATOC (Figure B).…”

Section: Introductionmentioning

confidence: 97%

“…Its applicability to the solid-phase peptide synthesis was confirmed by synthesizing the p -COOH-Bn-DOTA-conjugated [Tyr 3 ]octreotide (TOC) analogue, DOTA-Bn-TOC ( Figure 2 A). 29 The stability of [ 67 Ga]Ga-DOTA-Bn-TOC ( Figure 2 A) was compared with [ 67 Ga]Ga-DOTATOC ( Figure 2 B). Future perspectives and problems of bifunctional DOTA derivatives providing highly stable 68 Ga-labeled probes will be discussed.…”

Section: Introductionmentioning

confidence: 99%

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Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

et al. 2022

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Tetraazacyclododecane-1,4,7-triacetic acid (DO3A) has been used to prepare 68 Ga-labeled probes for the diagnostic counterpart of radiotheranostic applications. While DO3A provides stable complexes with therapeutic radionuclides such as 90 Y, 177 Lu, and 225 Ac, further improvement of the in vivo stability of the Ga-DO3A complex is required. Considering the high stability of an intact Ga-DOTA complex, the stability of Ga complexes of DOTA and DO3A derivatives, including benzyl-DOTA (Bn-DOTA), was evaluated to gain fundamental knowledge for developing the next-generation radiotheranostic probes using 68 Ga as a diagnostic counterpart. Following the complexation reaction to prepare 67 Ga-labeled DOTA and DO3A derivatives, the stability of the resulting 67 Ga-labeled compounds was evaluated in murine plasma and apo-transferrin challenge. [ 67 Ga]Ga-Bn-DOTA produced two isomers, and one of the isomers exhibited the highest stability among the tested complexes. The X-ray crystallography showed that the less stable isomer of Ga-Bn-DOTA suggested an N 3 O 3 coordination geometry, while Ga-DOTA and Ga-Bn-DO3A show N 4 O 2 coordination. To further evaluate the stability, a synthetic somatostatin analogue, [Tyr 3 ]octreotide (TOC), was used as a model peptide, and p-COOH-Bn-DOTA and DO3A were conjugated with TOC to prepare DOTA-Bn-TOC and DOTATOC.[ 67 Ga]Ga-DOTA-Bn-TOC also yielded two isomers with varying stability, and one isomer exhibited significantly higher stability than [ 67 Ga]Ga-DOTATOC both in vitro and in vivo. These findings indicate that para-substituted Bn-DOTA would constitute a suitable chelating agent for developing next-generation radiotheranostic probes, although high-performance liquid chromatography purification is needed. Thus, further chemical modification on the Bn-DOTA molecule is also needed to avoid the formation of a Ga complex with the N 3 O 3 configuration.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

et al. 2022

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“…Our previous study suggested that the physicochemical properties of radiometabolites play a crucial role in reducing renal radioactivity levels . Our recent study also showed that a 111 In-labeled D-phenylalanine conjugated-DOTA derivative was rapidly cleared from the kidneys when liberated from a parental octreotide analogue . These results suggested that [ 111 In]In-DOTA-Bn-F (Figure ) could be a radiometabolite suitable for the renal brush border strategy.…”

Section: Introductionmentioning

confidence: 99%

Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

Suzuki,

Araki,

Tatsugi

et al. 2023

J. Med. Chem.

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Synthesis and evaluation of a para-carboxylated benzyl-DOTA for labeling peptides and polypeptides

Cited by 2 publications

References 30 publications

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

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Synthesis and evaluation of a para-carboxylated benzyl-DOTA for labeling peptides and polypeptides

Cited by 2 publications

References 30 publications

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Reduction of the Renal Radioactivity of 111In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

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Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes