Substrate Study for Dihydroxyboryl Astatine Substitution Reaction with Fibroblast Activation Protein Inhibitor (FAPI)

Aso, Ayaka; Kaneda-Nakashima, Kazuko; Nabetani, H.; Kadonaga, Yuichiro; Shirakami, Yoshifumi; Watabe, Tadashi; Yoshiya, Taku; Mochizuki, Masahito; Koshino, Yuki; Ooe, Kazuhiro; Kawakami, Atsuko; Jinno, Naoya; Toyoshima, Atsushi; Haba, Hiromitsu; Wang, Yan; Cardinale, Jens; Giesel, Frederik L.; Shimoyama, Atsushi; Fukase, Koichi

doi:10.1246/cl.220391

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…Because 211 At could retain more compounds in tumors than 131 I, we conducted a therapeutic experiment using 211 At-FAPI1 and 5. Although the data are not shown in this article, it has been confirmed that FAPI uptake into cells is competitively inhibited when an unlabeled FAPI compound is present in excess [24]. Because labeling with 131 I was inefficient, the possibility that excess unlabeled substances were mixed with the labeled products cannot be ruled out.…”

Section: Discussionmentioning

confidence: 68%

“…They also claimed that no toxicity was observed in the kidneys, liver, stomach, or thyroid tissue. We also synthesized 211 At-FAPI(s) using dihydroxyboryl astatine substitution reaction [24]. We have previously established an astatination method that does not require toxic reagents [24,25].…”

Section: Introductionmentioning

confidence: 99%

“…We also synthesized 211 At-FAPI(s) using dihydroxyboryl astatine substitution reaction [24]. We have previously established an astatination method that does not require toxic reagents [24,25]. In this study, we investigated the usefulness of 211 At-FAPI(s) synthesized using an established safe method and a linker in the FAPI structure.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Aso

Nabetani

Matsuura

et al. 2023

IJMS

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Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Aso

Nabetani

Matsuura

et al. 2023

IJMS

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Development of a Neopentyl ²¹¹At‐Labeled Activated Ester Providing In Vivo Stable ²¹¹At‐Labeled Antibodies for Targeted Alpha Therapy

Tada,

Kaizuka,

Kannaka

et al. 2024

ChemMedChem

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In this study we developed a neopentyl 211At‐labeled activated ester that incorporates a triazole spacer and applied it to the synthesis of an 211At‐labeled cetuximab. The activated ester was synthesized via the nucleophilic 211At‐astatination of a neopentyl sulfonate carrying two long alkyl chains that serve as a lipid tag, which was followed by the hydrolysis of an acetal. Additionally, we developed a novel Resin‐Assisted Purification and Deprotection (RAPD) protocol involving a solid‐phase extraction of the protected 211At‐labeled compound from the mixture of the labeling reaction, hydrolysis of the acetal on the resin, and finally an elution of the 211At‐labeled activator from the resin. This method allows the synthesis of an 211At‐labeled activated ester with high purity through a simplified procedure that circumvents the need for HPLC purification. Using this 211At‐labeled activated ester, we efficiently synthesized 211At‐labeled cetuximab in 27±1% radiochemical yield with 95% radiochemical purity. This 211At‐activated ester demonstrated high reactivity, and enabled the completion of the reaction with the antibody within 10 min. In comparative biodistribution studies between 211At‐labeled cetuximab and the corresponding 125I‐labeled cetuximab in normal mice, both the thyroid and stomach showed radioactivity levels that were less than 1.0% of the injected dose.

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Fibroblast Activation Protein Inhibitor Theranostics

et al. 2023

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Substrate Study for Dihydroxyboryl Astatine Substitution Reaction with Fibroblast Activation Protein Inhibitor (FAPI)

Cited by 6 publications

References 17 publications

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Development of a Neopentyl ²¹¹At‐Labeled Activated Ester Providing In Vivo Stable ²¹¹At‐Labeled Antibodies for Targeted Alpha Therapy

Fibroblast Activation Protein Inhibitor Theranostics

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Substrate Study for Dihydroxyboryl Astatine Substitution Reaction with Fibroblast Activation Protein Inhibitor (FAPI)

Cited by 6 publications

References 17 publications

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

Development of a Neopentyl 211At‐Labeled Activated Ester Providing In Vivo Stable 211At‐Labeled Antibodies for Targeted Alpha Therapy

Fibroblast Activation Protein Inhibitor Theranostics

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Product

Resources

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Development of a Neopentyl ²¹¹At‐Labeled Activated Ester Providing In Vivo Stable ²¹¹At‐Labeled Antibodies for Targeted Alpha Therapy