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Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy

BACKGROUND: A family of BF(2)-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynam...

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Autores principales: Kawamura, Kazunori, Yamasaki, Tomoteru, Fujinaga, Masayuki, Kokufuta, Tomomi, Zhang, Yiding, Mori, Wakana, Kurihara, Yusuke, Ogawa, Masanao, Tsukagoe, Kaito, Nengaki, Nobuki, Zhang, Ming-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352184/
https://www.ncbi.nlm.nih.gov/pubmed/37458904
http://dx.doi.org/10.1186/s41181-023-00199-y
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author Kawamura, Kazunori
Yamasaki, Tomoteru
Fujinaga, Masayuki
Kokufuta, Tomomi
Zhang, Yiding
Mori, Wakana
Kurihara, Yusuke
Ogawa, Masanao
Tsukagoe, Kaito
Nengaki, Nobuki
Zhang, Ming-Rong
author_facet Kawamura, Kazunori
Yamasaki, Tomoteru
Fujinaga, Masayuki
Kokufuta, Tomomi
Zhang, Yiding
Mori, Wakana
Kurihara, Yusuke
Ogawa, Masanao
Tsukagoe, Kaito
Nengaki, Nobuki
Zhang, Ming-Rong
author_sort Kawamura, Kazunori
collection PubMed
description BACKGROUND: A family of BF(2)-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring. Radiolabeled photosensitizers can efficiently address photosensitizer biodistribution, providing helpful information for photodynamic therapy planning. To evaluate the biodistribution of ADPM06 and predict its pharmacokinetics on photodynamic therapy with light irradiation immediately after administration, we synthesized [(18)F]ADPM06 and evaluated its in vivo properties. RESULTS: [(18)F]ADPM06 was automatically synthesized by Lewis acid-assisted isotopic (18)F-(19)F exchange using ADPM06 and tin (IV) chloride at room temperature for 10 min. Radiolabeling was carried out using 0.4 μmol of ADPM06 and 200 μmol of tin (IV) chloride. The radiosynthesis time was approximately 60 min, and the radiochemical purity was > 95% at the end of the synthesis. The decay-corrected radiochemical yield from [(18)F]F(−) at the start of synthesis was 13 ± 2.7% (n = 5). In the biodistribution study of male ddY mice, radioactivity levels in the heart, lungs, liver, pancreas, spleen, kidney, small intestine, muscle, and brain gradually decreased over 120 min after the initial uptake. The mean radioactivity level in the thighbone was the highest among all organs investigated and increased for 120 min after injection. Upon co-injection with ADPM06, the radioactivity levels in the blood and brain significantly increased, whereas those in the heart, lung, liver, pancreas, kidney, small intestine, muscle, and thighbone of male ddY mice were not affected. In the metabolite analysis of the plasma at 30 min post-injection in female BALB/c-nu/nu mice, the percentage of radioactivity corresponding to [(18)F]ADPM06 was 76.3 ± 1.6% (n = 3). In a positron emission tomography study using MDA-MB-231-HTB-26 tumor-bearing mice (female BALB/c-nu/nu), radioactivity accumulated in the bone at a relatively high level and in the tumor at a moderate level for 60 min after injection. CONCLUSIONS: We synthesized [(18)F]ADPM06 using an automated (18)F-labeling synthesizer and evaluated the initial uptake and pharmacokinetics of ADPM06 using biodistribution of [(18)F]ADPM06 in mice to guide photodynamic therapy with light irradiation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-023-00199-y.
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spelling pubmed-103521842023-07-19 Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy Kawamura, Kazunori Yamasaki, Tomoteru Fujinaga, Masayuki Kokufuta, Tomomi Zhang, Yiding Mori, Wakana Kurihara, Yusuke Ogawa, Masanao Tsukagoe, Kaito Nengaki, Nobuki Zhang, Ming-Rong EJNMMI Radiopharm Chem Research Article BACKGROUND: A family of BF(2)-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring. Radiolabeled photosensitizers can efficiently address photosensitizer biodistribution, providing helpful information for photodynamic therapy planning. To evaluate the biodistribution of ADPM06 and predict its pharmacokinetics on photodynamic therapy with light irradiation immediately after administration, we synthesized [(18)F]ADPM06 and evaluated its in vivo properties. RESULTS: [(18)F]ADPM06 was automatically synthesized by Lewis acid-assisted isotopic (18)F-(19)F exchange using ADPM06 and tin (IV) chloride at room temperature for 10 min. Radiolabeling was carried out using 0.4 μmol of ADPM06 and 200 μmol of tin (IV) chloride. The radiosynthesis time was approximately 60 min, and the radiochemical purity was > 95% at the end of the synthesis. The decay-corrected radiochemical yield from [(18)F]F(−) at the start of synthesis was 13 ± 2.7% (n = 5). In the biodistribution study of male ddY mice, radioactivity levels in the heart, lungs, liver, pancreas, spleen, kidney, small intestine, muscle, and brain gradually decreased over 120 min after the initial uptake. The mean radioactivity level in the thighbone was the highest among all organs investigated and increased for 120 min after injection. Upon co-injection with ADPM06, the radioactivity levels in the blood and brain significantly increased, whereas those in the heart, lung, liver, pancreas, kidney, small intestine, muscle, and thighbone of male ddY mice were not affected. In the metabolite analysis of the plasma at 30 min post-injection in female BALB/c-nu/nu mice, the percentage of radioactivity corresponding to [(18)F]ADPM06 was 76.3 ± 1.6% (n = 3). In a positron emission tomography study using MDA-MB-231-HTB-26 tumor-bearing mice (female BALB/c-nu/nu), radioactivity accumulated in the bone at a relatively high level and in the tumor at a moderate level for 60 min after injection. CONCLUSIONS: We synthesized [(18)F]ADPM06 using an automated (18)F-labeling synthesizer and evaluated the initial uptake and pharmacokinetics of ADPM06 using biodistribution of [(18)F]ADPM06 in mice to guide photodynamic therapy with light irradiation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-023-00199-y. Springer International Publishing 2023-07-17 /pmc/articles/PMC10352184/ /pubmed/37458904 http://dx.doi.org/10.1186/s41181-023-00199-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kawamura, Kazunori
Yamasaki, Tomoteru
Fujinaga, Masayuki
Kokufuta, Tomomi
Zhang, Yiding
Mori, Wakana
Kurihara, Yusuke
Ogawa, Masanao
Tsukagoe, Kaito
Nengaki, Nobuki
Zhang, Ming-Rong
Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title_full Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title_fullStr Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title_full_unstemmed Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title_short Automated radiosynthesis and in vivo evaluation of (18)F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
title_sort automated radiosynthesis and in vivo evaluation of (18)f-labeled analog of the photosensitizer adpm06 for planning photodynamic therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352184/
https://www.ncbi.nlm.nih.gov/pubmed/37458904
http://dx.doi.org/10.1186/s41181-023-00199-y
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