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Article

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

1
Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science (iQMS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
2
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science (iQMS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
3
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
4
Japan Society for the Promotion of Science (JSPS), 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Valentina Gandin
Int. J. Mol. Sci. 2021, 22(9), 4622; https://doi.org/10.3390/ijms22094622
Received: 24 March 2021 / Revised: 20 April 2021 / Accepted: 26 April 2021 / Published: 28 April 2021
(This article belongs to the Section Molecular Biophysics)
Due to their short-range (2–500 nm), Auger electrons (Auger e) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e, it remains challenging to maximize the interaction between Auger e and DNA. To assess the DNA-damaging effect of Auger e released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e. View Full-Text
Keywords: Auger electron; cisplatin; 191Pt; 189Pt; radio-drug; DNA double-strand break; γH2AX Auger electron; cisplatin; 191Pt; 189Pt; radio-drug; DNA double-strand break; γH2AX
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MDPI and ACS Style

Obata, H.; Tsuji, A.B.; Sudo, H.; Sugyo, A.; Minegishi, K.; Nagatsu, K.; Ogawa, M.; Zhang, M.-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. Int. J. Mol. Sci. 2021, 22, 4622. https://doi.org/10.3390/ijms22094622

AMA Style

Obata H, Tsuji AB, Sudo H, Sugyo A, Minegishi K, Nagatsu K, Ogawa M, Zhang M-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. International Journal of Molecular Sciences. 2021; 22(9):4622. https://doi.org/10.3390/ijms22094622

Chicago/Turabian Style

Obata, Honoka, Atsushi B. Tsuji, Hitomi Sudo, Aya Sugyo, Katsuyuki Minegishi, Kotaro Nagatsu, Mikako Ogawa, and Ming-Rong Zhang. 2021. "In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons" International Journal of Molecular Sciences 22, no. 9: 4622. https://doi.org/10.3390/ijms22094622

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