@misc{oai:repo.qst.go.jp:00083682,
 author = {Honoka, Obata and Atsushi, Tsuji and Kotaro, Nagatsu and Mikako, Ogawa and Zhang, Ming-Rong and Honoka, Obata and Atsushi, Tsuji and Kotaro, Nagatsu and Mikako, Ogawa and Zhang, Ming-Rong},
 month = {Oct},
 note = {Aim/Introduction: Auger electrons (Auger e-
) have the 
potential for therapeutic applications by inducing nanoscale physiochemical damage to biomolecules due to 
their short-range (2-500 nm). Although DNA is the primary 
target of Auger e-
, it remains challenging to maximize the 
interaction between Auger e-
 and DNA. To assess the DNAdamaging efect of Auger e-
 released as close as possible 
to DNA, we focused on a platinum(Pt)-based antineoplastic 
drug, cisplatin, because it can form direct DNA adducts 
between Pt and nucleobases. Here, to evaluate the efect of 
Auger e-
 without chemical factors we radio-synthesized nocarrier-added (n.c.a.) [189, 191Pt]cisplatin (radio-cisplatin), and 
investigated its in vitro properties and DNA-damaging efect 
in cultured cells. Materials and Methods: N.c.a. radio-cisplatin 
was radio-synthesized by treating n.c.a. radio-PtCl4
2- with 
excess NH3
 and heating the reaction mixture, and the product 
was isolated by preparative HPLC. As in vitro evaluation of 
radio-cisplatin, cellular uptake, intracellular distribution, and 
DNA binding were investigated, and DNA double-strand 
breaks (DSBs) were evaluated by immunofuorescence 
staining of γH2AX. Results: Our production method provided 
n.c.a. radio-cisplatin with a radiochemical purity of 99% at the 
end of synthesis. Although uptake of radio-cisplatin was low 
(0.6% incubated dose after 25-h incubation), approximately 
20% of intracellular radio-Pt was in a nucleus, and 2% 
of intra-nucleus radio-Pt bound to DNA. Due to the low 
accumulation of radio-Pt, the frequency of cells with γH2AX 
foci was low (1%) in the γH2AX assays. Nevertheless, strong 
signals in nuclei of tumor cells treated with radio-cisplatin 
were found more often than with saline or nonradioactive 
cisplatin, suggesting Auger e-
 released very close to DNA 
cause more DSB. Conclusion: N.c.a. radio-cisplatin was 
successfully prepared at high radiochemical purities as an 
efective tool to evaluate DNA damage induced by Auger 
e-
 without chemical factors. Radio-cisplatin binding to DNA 
caused severe DSBs by the release of Auger e-
 very close 
to DNA without chemical damage by carriers. References:
Obata, et al. Int. J. Mol. Sci. 2021, 22, 4622. Obata, et al. Sci Rep 
2021, 11, 8140., EANM21(34th Annual Congress of the European Association of Nuclear Medicine)},
 title = {Production and in vitro evaluation of no-carrier-added  radio-cisplatin emitting Auger electrons},
 year = {2021}
}