6th Asia-Pacific Symposium on Radiochemistry September 17 ~ 22, 2017 • ICC Jeju • Jeju Island, Korea

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Gd Complex of DO3A-benzothiazole conjugates for image-guided Gd-NCT

Ki-Hye Jung1, Ji-Ae Park1, Jung Young Kim1, Hee-Kyoung Kim2, Kyo Chul Lee1, Kyeong Min Kim4 , Yongmin

Chang2,3,* , and Yong Jin Lee1,*,

1Division of RI-Convergence Research, Korea Institute of Radiological & Medical Science, Seoul, Korea 139-706

2Department of Medical & Biological Engineering, Kyungpook National University Daegu, Korea 702-701 3Department of Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea 700-721

Gd-DO3A-BTA has high potential for achieving magnetic resonance imaging (MRI) guided gadolinium neutron capture

therapy (GdNCT) of tumors. We have recently developed Gd(III) complex for targeting in tumor. The Gd-DO3A-BTA

showed a dramatically increased accumulation in tumors, leading to the selective contrast enhancement of tumor tissues

for precise tumor location by MRI. The accumulation of Gd in tumor site is effectively damage cancer cells by Gd-NCT.

We examined the neutron capture irradiation of MDA-MB-231 mice in the presence of Gd-DO3A-BTA. The results

indicate that Gd-DO3A-BTA is suitable neutron capture agent for Gd-NCT.

I. Introduction

Gadolinium neutron capture therapy (Gd-NCT) is a cancer therapy which utilized γ-rays and electron emitted by 157Gd (n, γ) 158Gd reaction to kill tumor cells. Gadolinium-157 has the very large thermal neutron capture cross section

(255000 barns). Moreover, the paramagnetic Gd(III) chelates, can enhance the contrast for MRI, which could be

exploited to delineate the outline and location of tumor for MR image-guided Gd-NCT. The aim of our present study is

to evaluate the feasibility of Gd-DO3A-BTA as MR image-guided Gd-NCT agent.

II. Results and Discussion

The Gd-DO3A-BTA i.v. injected MDA-MB-231 tumor-bearing mice, the tumor regions in mice exhibited enhanced

contrast (Figure 1a and b). The imaging results could provide accurate anatomical position of solid tumors for image-

guided thermal neutron irradiation, especially for local thermal neutron irradiation, thereby avoiding unnecessary

irradiation of normal tissues. The change in the tumor volume in the mice after the neutron irradiation is shown in Figure

1c and d. Without thermal neutron irradiation, Gd-DO3A-BTA affect tumor growth rates by antitumor activity of BTA,

and tumor volumes increased by over 15-fold at day 60. The Gd-DO3A-BTA injected and neutron irradiated group, the

tumor growth was significantly suppressed. It means tumor volume was less than 50%, compared with than in none Gd

administered and neutron irradiation group, 60 days after the neutron irradiation.

Figure 1. (a, b) in vivo MR images and CNR profiles of mice bearing MDA-MB-231 tumor obtained with Gd-DO3A-

BTA. (c) Tumor volume change of mice bearing subcutaneous MDA-MB-231 tumors after thermal neutron irradiation.

6th Asia-Pacific Symposium on Radiochemistry September 17 ~ 22, 2017 • ICC Jeju • Jeju Island, Korea

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III. Conclusions

We have presented a strategy for incorporating low-molecular-weight Gd(III) chelate for dual non-invasive MR

contrast agent and NCT. The Gd-DO3A-BTA had high therapeutic efficiency for Gd-NCT against solid tumors, as the

high accumulation of the Gd-DO3A-BTA in tumor tissues could effectively damage cancer cells by γ-rays or electron

emission from the Gd nuclides. We examined the neutron capture irradiation of MDA-MB-231 mice in the presence of

Gd-DO3A-BTA. The results indicate that Gd-DO3A-BTA is suitable MR image-guided neutron capture agent for Gd-

NCT.

ACKNOWLEDGMENTS

This research was supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS)

funded by the Ministry of Science, ICT & Future Planning, Republic of Korea.

(No.1711045578/1711045556/1711045577/1711045576/50532-2017)