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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

11.10.2023 | Original Article

Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (²¹¹At)

verfasst von: Hiroaki Echigo, Kenji Mishiro, Masayuki Munekane, Takeshi Fuchigami, Kohshin Washiyama, Kazuhiro Takahashi, Yoji Kitamura, Hiroshi Wakabayashi, Seigo Kinuya, Kazuma Ogawa

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2024

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Abstract

Purpose

We have developed probes for multiradionuclides radiotheranostics using RGD peptide ([⁶⁷Ga]Ga-DOTA-c[RGDf(4-I)K] ([⁶⁷Ga]1) and Ga-DOTA-[²¹¹At]c[RGDf(4-At)K] ([²¹¹At]2)) for clinical applications. The introduction of an albumin binding moiety (ABM), such as 4-(4-iodophenyl)-butyric acid (IPBA), that has high affinity with the blood albumin and prolongs the circulation half-life can improve the pharmacokinetics of drugs. To perform more effective targeted alpha therapy (TAT), we designed and synthesized Ga-DOTA-K([²¹¹At]APBA)-c(RGDfK) ([²¹¹At]5) with 4-(4-astatophenyl)-butyric acid (APBA), which has an astato group instead of an iodo group in IPBA. We evaluated whether APBA functions as ABM and [²¹¹At]5 is effective for TAT. In addition, we prepared ⁶⁷Ga-labeled RGD peptide without ABM, [⁶⁷Ga]Ga-DOTA-K-c(RGDfK) ([⁶⁷Ga]3), and ¹²⁵I-labeled RGD peptide with ABM, Ga-DOTA-K([¹²⁵I]IPBA)-c(RGDfK) ([¹²⁵I]4), to compare with [²¹¹At]5.

Methods

Biodistribution experiments of [⁶⁷Ga]3 without ABM, [¹²⁵I]4 and [²¹¹At]5 with ABM were conducted in normal mice and U-87 MG tumor-bearing mice. In addition, two doses of [²¹¹At]5 (370 or 925 kBq) were administered to U-87 MG tumor-bearing mice to confirm the therapeutic effects.

Results

The blood retention of [¹²⁵I]4 and [²¹¹At]5 was remarkably increased compared to [⁶⁷Ga]3. Also, [¹²⁵I]4 and [²¹¹At]5 showed similar biodistribution and significantly greater tumor accumulation and retention compared to [⁶⁷Ga]3. In addition, [²¹¹At]5 inhibited tumor growth in a dose-dependent manner.

Conclusion

The functionality of APBA as ABM like IPBA, and the usefulness of [²¹¹At]5 as the radionuclide therapy agent for TAT was revealed.

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Titel: Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At)
verfasst von: Hiroaki Echigo
Kenji Mishiro
Masayuki Munekane
Takeshi Fuchigami
Kohshin Washiyama
Kazuhiro Takahashi
Yoji Kitamura
Hiroshi Wakabayashi
Seigo Kinuya
Kazuma Ogawa
Publikationsdatum: 11.10.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06457-0

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (²¹¹At)

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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