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Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice

The platinum-based antineoplastic drug cisplatin is commonly used for chemotherapy in clinics. This work aims to demonstrate a radio-platinum tracer is useful for precisely quantifying small amounts of platinum in pharmacokinetics studies. METHODS: A cisplatin radiotracer (radio-cisplatin) was synth...

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Autores principales: Obata, Honoka, Tsuji, Atsushi B., Sudo, Hitomi, Sugyo, Aya, Minegishi, Katsuyuki, Nagatsu, Kotaro, Ogawa, Mikako, Zhang, Ming-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575570/
https://www.ncbi.nlm.nih.gov/pubmed/36120823
http://dx.doi.org/10.1097/MNM.0000000000001614
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author Obata, Honoka
Tsuji, Atsushi B.
Sudo, Hitomi
Sugyo, Aya
Minegishi, Katsuyuki
Nagatsu, Kotaro
Ogawa, Mikako
Zhang, Ming-Rong
author_facet Obata, Honoka
Tsuji, Atsushi B.
Sudo, Hitomi
Sugyo, Aya
Minegishi, Katsuyuki
Nagatsu, Kotaro
Ogawa, Mikako
Zhang, Ming-Rong
author_sort Obata, Honoka
collection PubMed
description The platinum-based antineoplastic drug cisplatin is commonly used for chemotherapy in clinics. This work aims to demonstrate a radio-platinum tracer is useful for precisely quantifying small amounts of platinum in pharmacokinetics studies. METHODS: A cisplatin radiotracer (radio-cisplatin) was synthesized, and a comprehensive evaluation of cisplatin over 7 days after its intravenous injection into nude mice bearing a subcutaneous lung tumor (H460) was conducted. RESULTS: A biphasic retention curve in the whole body and blood was observed [T(1/2)(α) = 1.14 h, T(1/2)(β) = 5.33 days for the whole body, and T(1/2)(α) = 23.9 min, T(1/2)(β) = 4.72 days for blood]. The blood concentration decreased within 1 day after injection. Most of the intact cisplatin was excreted via the kidneys in the early time points, and a small part was distributed in tissues including tumors. The plasma protein binding rate of cisplatin increased rapidly after injection, and the protein-bound cisplatin remained in the blood longer than intact cisplatin. The peak uptake in H460 tumors was 4.7% injected dose per gram at 15 min after injection, and the area under the curve (AUC(0–7 days)) was approximately one-half to one-third of the AUC(0–7 days) in the kidneys, liver, and bone, where some toxicity is observed in humans. CONCLUSION: The radio-platinum tracer revealed the highly quantitative biodistribution of cisplatin, providing insights into the properties of cisplatin, including its adverse effects. The tracer enables a precise evaluation of pharmacokinetics for platinum-based drugs with high sensitivity.
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spelling pubmed-95755702022-10-19 Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice Obata, Honoka Tsuji, Atsushi B. Sudo, Hitomi Sugyo, Aya Minegishi, Katsuyuki Nagatsu, Kotaro Ogawa, Mikako Zhang, Ming-Rong Nucl Med Commun Original Articles The platinum-based antineoplastic drug cisplatin is commonly used for chemotherapy in clinics. This work aims to demonstrate a radio-platinum tracer is useful for precisely quantifying small amounts of platinum in pharmacokinetics studies. METHODS: A cisplatin radiotracer (radio-cisplatin) was synthesized, and a comprehensive evaluation of cisplatin over 7 days after its intravenous injection into nude mice bearing a subcutaneous lung tumor (H460) was conducted. RESULTS: A biphasic retention curve in the whole body and blood was observed [T(1/2)(α) = 1.14 h, T(1/2)(β) = 5.33 days for the whole body, and T(1/2)(α) = 23.9 min, T(1/2)(β) = 4.72 days for blood]. The blood concentration decreased within 1 day after injection. Most of the intact cisplatin was excreted via the kidneys in the early time points, and a small part was distributed in tissues including tumors. The plasma protein binding rate of cisplatin increased rapidly after injection, and the protein-bound cisplatin remained in the blood longer than intact cisplatin. The peak uptake in H460 tumors was 4.7% injected dose per gram at 15 min after injection, and the area under the curve (AUC(0–7 days)) was approximately one-half to one-third of the AUC(0–7 days) in the kidneys, liver, and bone, where some toxicity is observed in humans. CONCLUSION: The radio-platinum tracer revealed the highly quantitative biodistribution of cisplatin, providing insights into the properties of cisplatin, including its adverse effects. The tracer enables a precise evaluation of pharmacokinetics for platinum-based drugs with high sensitivity. Lippincott Williams & Wilkins 2022-11 2022-09-19 /pmc/articles/PMC9575570/ /pubmed/36120823 http://dx.doi.org/10.1097/MNM.0000000000001614 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Original Articles
Obata, Honoka
Tsuji, Atsushi B.
Sudo, Hitomi
Sugyo, Aya
Minegishi, Katsuyuki
Nagatsu, Kotaro
Ogawa, Mikako
Zhang, Ming-Rong
Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title_full Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title_fullStr Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title_full_unstemmed Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title_short Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
title_sort precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575570/
https://www.ncbi.nlm.nih.gov/pubmed/36120823
http://dx.doi.org/10.1097/MNM.0000000000001614
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