Copper-mediated radioiodination and radiobromination via aryl boronic precursor and its application to 125I/77Br–labeled prostate-specific membrane antigen imaging probes

Kondo, Yuto; Kimura, Hiroyuki; Sasaki, Iwao; Watanabe, Shigeki; Ohshima, Yasuhiro; Yagi, Yusuke; Hattori, Yoshiyuki; Koda, Manami; Kawashima, Hidekazu; Yasui, Hirofumi; Ishioka, Noriko S.

doi:10.1016/j.bmc.2022.116915

Cited by 8 publications

(14 citation statements)

References 18 publications

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“…The radiobromination method was observed to be amenable to a variety of aryl and heteroaryl compounds with varying steric and electronic substituents. Compared with previous deboro-radiobromination reports, , the method is effective with milder conditions, less precursor, and more radioactivity, as evidenced over a wide substrate scope. The utility of the developed methodology is demonstrated by synthesis of three radiobrominated medicinal targeted molecules with moderate to high yields and theranostic potential.…”

Section: Discussionmentioning

confidence: 80%

“…Furthermore, this work has been adapted for the incorporation of 123 I and 211 At by the Gouverneur and Mach groups, respectively. While copper-mediated coupling of boronic pinacol esters ,, /acids , has facilitated incorporation of 77 Br into a small selection of molecules, a systematic investigation of a general procedure for labeling (hetero)aryl boronic pinacol esters with radiobromine has yet to be reported. One of the challenges of these methods has been highlighted in radiofluorination wherein the cyclotron-produced [ 18 F]fluoride (aq) must be concentrated through the use of a quaternary methylammonium (QMA) cartridge prior to deborylfluorination radiochemistry.…”

Section: Introductionmentioning

confidence: 99%

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Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

et al. 2023

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A copper-mediated radiobromination of (hetero)aryl boronic pinacol esters is described. Cyclotron-produced [ 76/77 Br]bromide was isolated using an anion exchange cartridge, wherein the pre-equilibration and elution solutions played a critical role in downstream deboro-bromination. The bromination tolerates a broad range of functional groups, labeling molecules with ranging electronic and steric effects. Bologically active radiopharmaceuticals were synthesized, including two radiobrominated inhibitors of poly ADP ribose polymerase, a clinically relevant chemotherapeutic target for ovarian, breast, and prostate cancers.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

et al. 2023

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“…The target compounds ([ 125 I] 2 and [ 125 I] 4 ) were synthesized as shown in Figure . The radiolabeling protocol was prepared according to previously reported methods with some modifications. − In this study, Cu(py) 4 (OTf) 2 (py = pyridine, OTf = trifluoromethanesulfonate) was used as it was reported as the optimal copper catalyst for this labeling reaction . A boronic precursor ( 1 or 3 ) and Cu(py) 4 (OTf) 2 dissolved in a solvent, water (H 2 O), or an organic solvent to control the H 2 O content of the reaction solvent were added to a microtube in this precise order.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Copper-mediated nucleophilic reactions using a boronic precursor are promising radiosynthetic methods for labeling an aromatic ring with radioiodine. − Copper-mediated radioiododeboronation is performed in a reaction vessel exposed to air at room temperature, leading to the formation of the desired radiolabeled compound without the preparation of complex starting materials or reagents. In addition, copper-mediated radioiododeboronation can also be adapted for direct radiolabeling of peptide mimetics. , Thus, it solves the issues of classical direct radiolabeling of peptides using radioiododestannylation or electrophilic radioiodination of tyrosine residues, such as toxicity of the organotin precursor or formation of byproducts . However, information for optimizing reaction conditions for various peptides is ambiguous, as the method has scarcely been used for this type of compounds.…”

Section: Introductionmentioning

confidence: 99%

Effect of Water on Direct Radioiodination of Small Molecules/Peptides Using Copper-Mediated Iododeboronation in Water–Alcohol Solvent

et al. 2023

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Direct radioiodination of peptides using copper-mediated iododeboronation is a promising radiosynthetic method for solving issues of classical direct radiolabeling, such as toxicity of the organotin precursor (iododestannylation) or formation of radio byproducts (by electrophilic iodination of a tyrosine residue). However, the parameters for optimizing the reaction conditions for various peptides are not completely understood. In particular, considering peptide solubility, the effects of water-containing solvents on labeling efficiency should be thoroughly investigated. Herein, we describe the effect of water on copper-mediated radioiododeboronation and the key factors for ensuring the successful radiolabeling of small molecules and peptides in water–organic solvents. 125I-labeled substrates containing peptides ([125I]m/p-IBTA) were obtained with high radiochemical conversions (RCCs: >95%) using an alcohol solvent, and a decrease in these RCCs was observed with increasing water content in the methanol solvent. Additionally, when using water–methanol solvents, a difference in RCC due to the substituent effect was also observed. However, the RCCs can be improved without the use of other additives by adjusting the copper catalyst and time of the labeling reaction or by utilizing substituent effects. This study contributes to the improvement of the design of boronic peptide precursors and radiolabeling protocols using copper-mediated iododeboronation.

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“…The polonium X-rays can be monitored by γ-cameras used in clinical diagnostic applications [3,27,28]. Iodine can, in many cases, be used as an analog to astatine for chemical optimization, and moreover, the iodine nuclides 123 I and 124 I are also relevant for diagnostic imaging applications [29][30][31]. Therefore, astatine and iodine could be used as a theranostic pair for combined therapy and imaging [32].…”

Section: Introductionmentioning

confidence: 99%

Pretargeted Alpha Therapy of Disseminated Cancer Combining Click Chemistry and Astatine-211

et al. 2023

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To enhance targeting efficacy in the radioimmunotherapy of disseminated cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with a modified monoclonal antibody that has an affinity for both tumor antigens and radiolabeled carriers. In this work, we aimed to synthesize and evaluate poly-L-lysine-based effector molecules for pretargeting applications based on the tetrazine and trans-cyclooctene reaction using 211At for targeted alpha therapy and 125I as a surrogate for the imaging radionuclides 123, 124I. Poly-L-lysine in two sizes was functionalized with a prosthetic group, for the attachment of both radiohalogens, and tetrazine, to allow binding to the trans-cyclooctene-modified pretargeting agent, maintaining the structural integrity of the polymer. Radiolabeling resulted in a radiochemical yield of over 80% for astatinated poly-L-lysines and a range of 66–91% for iodinated poly-L-lysines. High specific astatine activity was achieved without affecting the stability of the radiopharmaceutical or the binding between tetrazine and transcyclooctene. Two sizes of poly-L-lysine were evaluated, which displayed similar blood clearance profiles in a pilot in vivo study. This work is a first step toward creating a pretargeting system optimized for targeted alpha therapy with 211At.

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Copper-mediated radioiodination and radiobromination via aryl boronic precursor and its application to 125I/77Br–labeled prostate-specific membrane antigen imaging probes

Cited by 8 publications

References 18 publications

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

Copper-Mediated Radiobromination of (Hetero)Aryl Boronic Pinacol Esters

Effect of Water on Direct Radioiodination of Small Molecules/Peptides Using Copper-Mediated Iododeboronation in Water–Alcohol Solvent

Pretargeted Alpha Therapy of Disseminated Cancer Combining Click Chemistry and Astatine-211

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