III-3. Radiochemistry & Nuclear Chemistry

RIKEN Accel. Prog. Rep. 55 (2022)

RIKEN Accel. Prog. Rep. 55 (2022)

Eﬀect of tumor size on the therapeutic eﬀect of 67 Cu-labeled
compounds targeting the somatostatin receptor
Y. Fujisawa,∗1 H. Haba,∗2 A. Nambu,∗2 Y. Shigekawa,∗2 Y. Wang,∗2 X. Yin,∗2 Y. Magata,∗3 and Y. Iida∗1Nuclear medicine therapy, wherein a radiopharmaceutical is administered to patients for treatment, is aneﬀective medical treatment that targets cancer cells inthe body; it has garnered signiﬁcant attention in recent
years as an eﬀective treatment process that places lessburden on patients. Four nuclides are available in Japan,
namely, 131 I, 90 Y, and 177 Lu, which are β-particle emitting nuclides, and 223 Ra, which is an α-particle emitting
nuclide. 90 Y has a high energy β-particle of 2.28 MeV
and exhibits good therapeutic eﬀect; however, it has asigniﬁcant impact on the surrounding tissues and theinjected dose is limited by exposure to other organs.1)
Several other nuclides can be potentially used for nuclear
medicine therapy. For example, 67 Cu has a low energy
β-particle of 0.392 MeV; it can be administered in large
doses but its eﬀectiveness has not yet been suﬃciently
analyzed. Therefore, depending on the property of cancer tissue, eﬀective and eﬃcient treatment can be realized. It should be noted that the eﬀectiveness of nuclear
medicine therapy is aﬀected by the properties and size oftarget cancer tissue, radiation quality, and energy, suggesting that the most eﬃcient radiation energy may existfor each target.2) In other words, although the range oftherapeutic eﬀect is limited owing to low energy, suﬃcient eﬀects can be obtained with low-energy β-particles
for small tumors, thus leading to eﬀective treatment.3)
We previously synthesized 67 Cu-ToDBTTATE targetingthe somatostatin receptor and demonstrated that thiscompound constricts tumor growth in model mice bearing AR42J rat pancreatic tumor cells.4) Further investigations regarding the characteristics of 67 Cu may contribute to eﬀective and eﬃcient treatment and/or customized medicine according to patient conditions.
In this study, we prepared model mice with tumors ofvarious sizes and attempted to investigate the diﬀerencesin the therapeutic eﬀect of 67 Cu-ToDBTTATE on thetumor size to clarify the relationship between tumor size
and the therapeutic eﬀects of 67 Cu-ToDBTTATE.
Tumor-bearing mice were prepared by implanting
AR42J tumor cells (5 × 106 cells), in 0.1 mL PBS, into
the ﬂanks of nude mice (BALB/c-nu/nu, male). Afterthe tumor grew to various sizes, 16.0–25.2 MBq of 67 CuToDBTTATE was injected into the mice from the tailvein. Saline or non-labeled ToDBTTATE-administeredmice were used as the control. All mice were weighed
and the tumor diameters were regularly measured using a caliper; the tumor volumes were determined us∗1
∗2
∗3

Faculty of Pharmaceutical Sciences, Suzuka University ofMedical Science
RIKEN Nishina Center
Department of Molecular Imaging, Hamamatsu University
School of Medicine

Fig. 1. Relationship between tumor size and the therapeutic eﬀect of 67 Cu-ToDBTTATE (◦: control, : 67 CuToDBTTATE). *: p < 0.05 (2-way ANOVA, sidack-test).

ing the following formula: (longer diameter) × (shorterdiameter)2 /2. This study was performed in accordancewith the recommendations by the Guide for the Careand Use of Laboratory Animals of Suzuka University ofMedical Science.
The mice were divided into four groups according tothe tumor size, i.e., less than 200, 200 to 400, 400 to600, and 600 to 800 mm3 ; then, the 67 Cu-ToDBTTATEadministered mice were compared with the control ineach group. A tumor growth constricting eﬀect was observed in the 67 Cu-ToDBTTATE-administered mice inall groups compared with the control (Fig. 1). Sometumor growth was observed in the group with a tumor
size of less than 200 mm3 , which may be because thedays after cell implantation were short and the targeted
somatostatin receptor was not well expressed. No difference in the therapeutic eﬀect of 67 Cu-ToDBTTATEon the tumor size was observed in this study. In future
works, we plan to conduct comparative studies using
model mice with larger tumors.
References1) G. A. Wiseman et al., Eur. J. Nucl. Med. 27, 766 (2000).
2) K. Fujimori et al., Kaku Igaku 31, 241 (1994).
3) E. B. van Dieren et al., Int. J. Radiat. Oncol. Biol. Phys.
36, 197 (1996).
4) Y. Fujisawa et al., RIKEN Accel. Prog. Rep. 53, 175(2019).

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