Ⅲ-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 56 (2023)
RIKEN
Accel. Prog. Rep. 56 (2023)

Eﬃcacy of nuclear medicine therapy with 67 CuCl2 in mice bearing
LS180 colon cancer
Y. Fujisawa,∗1 Y. Sugiura,∗1 H. Haba,∗2 A. Nambu,∗2 Y. Shigekawa,∗2 X. Yin,∗2 Y. Magata,∗3 and Y. Iida∗167CuCl2 intravenously. Saline-treated mice were used
as a control. Mice were weighed and tumor diameters were recorded regularly. The diameters of tumorswere measured with a caliper, and tumor volumes
were determined using the formula: (longer diameter)× (shorter diameter)2 /2. This study was performedin accordance with the recommendations by the Guidefor the Care and Use of Laboratory Animals of theSuzuka University of Medical Science.
67
CuCl2 showed high accumulation in the tumor,
6.50 ± 2.34, 6.85 ± 1.83, and 5375 ± 1.26% ID/g at
1, 24, and 48 h after administration, as shown in aprevious study. Tumor size reduction was observed in
all mice treated with 67 CuCl2 (Fig. 1). However, but
relatively signiﬁcant weight loss was also observed inthem (Fig. 2). Therefore, 67 Cu is a promising RI for

3t u m o r v o lu m e ( m m )

4000

3000

2000

1000

*

*

002468101214d a y s a f te r a d m in is t r a tio nFig. 1. Therapeutic studies of 67 CuCl2 in LS180 tumorbearing mice. (•; saline (n = 7), △; 67 CuCl2 (n = 4).
*, p < 0.05 (2-way ANOVA followed by sidack-test).

1 .1b o d y w e ig h t r a t io

Nuclear medicine is one of the eﬀective methods forearly diagnosis and therapy of cancer, and various radioisotopes (RI) have been used. Among them, radioactive Cu is expected to be a promising RI withdiagnostic and therapeutic properties. Radioactive Cu
includes 60 Cu, 61 Cu, 62 Cu, and 64 Cu, which are eﬀective for PET diagnosis, and 67 Cu, which can be applied
for treatment. 67 Cu is a therapeutic radionuclide thatemits β-particles of energy 0.392 to 0.577 MeV with ahalf-life of 61.8 h. Although the β-particle energy of67Cu is low, it is expected to be eﬀective in treatingsmall cancers.1) RIs that have high-energy β-particles,
such as 90 Y, show a good therapeutic eﬀect, but theyalso have a large eﬀect on surrounding tissues, andthe injected dose is limited by exposure to other organs.2) 67 Cu has a low-energy β-particles and can beadministered in large doses, leading to eﬀective and efﬁcient treatment.3) Another advantage of 67 Cu is theability to calculate exposure doses accurately. Injected
doses of radiopharmaceuticals used in nuclear medicine
therapy are calculated from the exposure doses. 67 Culabeled drugs can accurately calculate the exposure
doses with 64 Cu-labeled ones, contributing to safe andeﬀective personalized medicine.
Various studies have been conducted on cancer diagnosis and therapy using radioactive Cu-labeled drugs,
and in recent years, the possibility of PET diagnosis
using 64 CuCl2 has been demonstrated. Copper transporter protein 1 (CTR1) is overexpressed in various
cancers, suggesting that 64 Cu accumulates in cancer
via CTR1.4) Based on these studies, the tumor accumulation of 67 CuCl2 was also evaluated, and it was
found to have the same pharmacokinetics as 64 CuCl2 .5)
In this study, we investigated the therapeutic eﬀect of67
CuCl2 on tumor-bearing mice to clarify the potentialof cancer therapy using 67 CuCl2 .
Tumor-bearing mice were prepared by implantationof LS180 tumor cells (5 × 106 cells) in 0.1 mL PBS
into the ﬂanks of nude mice (BALB/c-nu/nu, male).
Biodistribution experiments were performed by intravenously administering 67 CuCl2 . The mice were killed
at 1, 24 and 48 h after administration, and tissuesof interest were excised and weighed before their radioactivity was measured. LS180 tumors were grownin BALB/c mice in the same way for therapeutic studies. Mice were administered with 17.0–23.2 MBq of1 .00 .9

*
*0 .8

*

*0 .7024

68

101214d a y s a f te r a d m in is t r a tio n

∗1
∗2
∗3

Faculty of Pharmaceutical Sciences, Suzuka University ofMedical Science
RIKEN Nishina Center
Department of Molecular Imaging, Hamamatsu University
School of Medicine- 156 -Fig. 2. Changes in body weight of mice after saline or67
CuCl2 administration. (•; saline (n = 7), △; 67 CuCl2(n = 4). *, p < 0.05 (2-way ANOVA followed by sidacktest).

Ⅲ-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 56 (2023)

the treatment of cancer, but the use of 67 Cu-labeled
drugs that selectively accumulate in cancer cells arethought to be more suitable for cancer therapy.
References
1) Y. Fujisawa et al., RIKEN Accel. Prog. Rep. 53, 175(2019).
2) G. A. Wiseman et al., Eur. J. Nucl. Med. 27, 766 (2000).
3) Y. Fujisawa et al., RIKEN Accel. Prog. Rep. 55, 141(2021).
4) C. Qin et al., J. Nucl. Med. 55, 812 (2014).
5) Y. Sugo et al., J. Phys. Soc. Jpn. 86, 023201 (2017).

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