III-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 54 (2021)

RIKEN Accel. Prog. Rep. 54 (2021)

Quality conﬁrmation of RIKEN 186 Re using bifunctional chelatingagents and derivatives
S. Oshikiri,∗1,∗2 M. K. -Satake,∗1,∗2 H. Kato,∗1,∗2 Y. Komori,∗1 K. Suzuki,∗1,∗2 T. Kobayashi,∗2 A. Hino,∗2 andH. Haba∗1
Rhenium-186 (half-life T1/2 = 3.7186 days) and 188 Re(T1/2 = 17.003 hours) emit beta rays appropriate fortargeted radiotherapy use. These radioactive Re isotopes are used according to the tumor size and form
radiotheranostic pairs with 99m Tc for radiodiagnosis.1)
However, 186 Re has not been investigated as well as
188Re has.2) One of the possible reasons is that it isdiﬃcult to obtain no-carrier-added 186 Re through theclassical production method of the 185 Re(n, γ)186 Re reaction, while no-carrier-added 188 Re can be obtained using a 188 W/188 Re generator.1,3) At RIKEN, we started
to produce no-carrier-added 186 Re (RIKEN 186 Re) inthe 186 W(d, 2n)186 Re reaction at the RIKEN AVF cyclotron. In this study, we selected DADT, ECD, MAG3,and DMSA (Fig. 1) as model compounds, which had
already been reported in many articles,4–7) and evaluated radiolabeling eﬃciencies for these compounds toconﬁrm the quality of RIKEN 186 Re, especially in termsof its usefulness as a radioisotope (RI) material for bifunctional chelating agents and derivatives.8,9)
In this report, the method for DADT radiolabeling is
described below as the representative among the modelcompounds.
Step 1: RIKEN 186 Re (3.8 MBq) was dissolved in
0.05 M hydrochloric acid to prepare a 186 Re
stock solution (138 MBq/mL). The radioactivity of 186 Re was determined using a germanium
semiconductor detector and a dose calibrator.
Step 2: 2.2 µL of the 186 Re stock solution in Step 1 wasadded to 63.8 µL of saline to prepare a 186 Resolution.
Step 3: 3.0 µL of the 186 Re solution in Step 2 was mixed
with 2.5 µL of DADT (1.0 µg), 1.4 µL of tin (II)dichloride dihydrate (10 µg), and 2.0 µL of Ltartaric acid (200 µg) aqueous solution.
Step 4: The mixture in Step 3 was heated to 99◦ C andheld for 15 min.
Step 5: The radiolabeling yield of 186 Re-DADT wasdetermined using the TLC method with aC18 reversed-phase TLC plate (NAGEL RP18W/UV254) and eluted with acetone and
0.5 M ammonium acetate in a volume ratio of
13:7.
As a result, the radiolabeling yield of 186 Re-DADT at
the speciﬁc radioactivity of 4.3 GBq/mmol was 86%. In
Ref. 4), 88% of the radiolabeling yield of 188 Re-DADTat the speciﬁc radioactivity of 23 GBq/mmol was reported. To compare these results, each activity of 186 Re
and 188 Re was converted to the amount of substance.
∗1∗2

RIKEN Nishina Center
RI Research Department, FUJIFILM Toyama Chemical Co.,
Ltd.

NH HN

EtOOCNH HN

SH HS

SH HS

DADT

ECD

COOEt

OO

NH HN
SH HN

O

HS

COOH

HS

COOH

COOH

MAG3

DMSA

Fig. 1. Chemical structures of DADT, ECD, MAG3 , andDMSA.

Both 4.3 GBq of 186 Re and 23 GBq of 188 Re correspondto 3.3 nmol. This indicates that the ratio of the amountof DADT to that of 186/188 Re was constant. Therefore,
it was regarded that our result of labeling yield corresponded to that of 188 Re in Ref. 4). In a previous invivo and in vitro evaluation, the radiolabeling of 222MAMA(N -6-Ahx-OEt) with 186 Re was performed on6.1 GBq/mmol.10) It was suggested that RIKEN 186 Re
is useful as an RI material for in vivo and in vitro studies.
Regarding the radiolabeling eﬃciencies for ECD,
MAG3 , and DMSA, the radiolabeling yields were 51%,46%, and 95%, respectively. It was revealed that thesecompounds are also able to form 186 Re complexes, although these are preliminary results.
In conclusion, our study revealed the availability ofRIKEN 186 Re for radiolabeling and its feasibility as
an RI material with bifunctional chelating agents andderivatives. By optimizing the labeling conditions in thefuture, RIKEN 186 Re is expected to be applied to targeted radiotherapy using bifunctional chelating agents,
such as a peptide moiety in their structures.11)
References
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2) L. Uccelli et al., Molecules 24, 640 (2019).
3) G. Makris et al., Mol. Imaging Biol. 23, 52 (2021).
4) J. M. Jeong et al., Nucl. Med. Biol. 28, 197 (2001).
5) T. -Y. LuO et al., Nucl. Med. Biol. 31, 671 (2004).
6) G. W. Visser et al., J. Nucl. Med. 34, 1953 (1993).
7) K. Kothari et al., Appl. Rad. Iso. 51, 43 (1999).
8) G. Liu et al., Anticancer Agents Med. Chem. 7, 367(2007).
9) U. Choudhry et al., Dalton Trans. 3, 311 (2003).
10) D. W. Demoin et al., Nucl. Med. Biol. 43, 802 (2016).
11) V. A. Sanders et al., Nucl. Med. Biol. 68–69, 1 (2019).

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