Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a 10BSH-containing WOW emulsion

doi:10.1016/j.apradiso.2014.01.014

Applied Radiation and Isotopes

Volume 88, June 2014, Pages 32-37

https://doi.org/10.1016/j.apradiso.2014.01.014 Get rights and content

Highlights

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We started the pilot clinical study of BNCT to recurrence hepatic cancer.
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The tumor size was remained stable during 3 months after BNCT(SD).
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No adverse effect as a result of BNCT was observed during follow-up period.
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¹⁰B-containing WOW emulsion can be applied as a novel intra-arterial boron carrier for BNCT for HCC.

Abstract

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a ¹⁰BSH-containing water-in-oil-in-water emulsion (¹⁰BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that ¹⁰BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC.

Introduction

The cytotoxic effects of boron neutron capture therapy (BNCT) are due to a nuclear reaction between ¹⁰B atoms and thermal neutrons. The α particles and ⁷Li ions that arise from the abovementioned capture reaction damage any cell structures located within a path length of about 10 μm. So, it is very important to develop selective boron delivery systems for effective BNCT (Yanagie and Tomita, 1997, Yanagie and Maruyama, 2006, 2008). We would like to use BNCT to treat radioresistant tumors, such as locally advanced or locally recurrent breast cancer, hepatocellular carcinoma (HCC), metastatic liver tumors, and lung cancer (Yanagië and Ogata, 2008, Yanagie and Kumada, 2011).

Most HCC are considered to be incurable, and there are few treatment options for prolonging survival. Iodized poppy-seed oil (IPSO) is selectively deposited in HCC cells. Suzuki and Masunaga, 2000, Suzuki and Masunaga, 2004, Suzuki and Sakurai, 2007 reported that the intra-arterial administration of a boron compound mixed with IPSO is technically a form of chemo-embolization, which has been widely used in the treatment of liver tumors. They also reported the clinical results of the first patient with multiple HCC to be treated with BNCT. Higashi et al. (1995) prepared a long-term inseparable water-in-oil-in-water emulsion (WOW) containing 8–60 mg of epirubicin for use in arterial injection therapy for patients with HCC. The WOW was prepared using a membrane emulsification technique involving a controlled pore glass membrane. Emulsification using a fine-pore glass membrane with pores of a defined size (i.e., a controlled-pore glass membrane) is a new technique for preparing lipid microdroplets of equal size (monodispersed) containing fine aqueous microdroplets, which can be used to produce WOW emulsions.

Here, we present a new protocol for BNCT for HCC, which could be an option for patients who cannot be treated with conventional therapies. In this study, we developed a boron compound-containing WOW emulsion and evaluated its toxicity to the human body as well as the efficiency of tumor growth suppression by BNCT involving the intra-arterial injection of the WOW emulsion.

Section snippets

Human subject protection

This pilot study was reviewed and approved by the institutional review board of Kojin-kai Medical City East Hospital, Japan. In addition, the institutional review board of Kyoto University Research Reactor Institute (KURRI), Japan, judged the eligibility of each patient for this pilot study.

Case presentation

A 63-year-old man underwent right lobectomy of the liver (not involving segment 5) in October 2006. The patient received eight rounds of trans-catheter arterial chemotherapy involving an

Discussion

HCC is difficult to cure regardless of whether surgery, chemotherapy, or radiotherapy is employed. However, IPSO is selectively deposited in HCC cells, and mixing IPSO with water-soluble anti-tumor agents has been demonstrated to be useful for detecting and treating liver cancer. In addition, styrene maleic acid neocarzinostatin, a lipophilic high molecular weight anticancer agent, dispersed in IPSO has also been used to target chemotherapy for HCC. Thus, injecting chemotherapeutic agents in

Conclusions

We started a pilot clinical study of BNCT for recurrent HCC. The size of the tumorous region remained stable during the 3 months after the BNCT (stable disease). No adverse effects of the BNCT were observed during the treatment or follow-up period. The present results demonstrate that ¹⁰B-containing WOW emulsions can be used as novel intra-arterial boron carriers during BNCT for HCC.

Acknowledgments

This study was supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan (Nos. 18390360 and 24390311 to Hironobu Yanagie), a Grant-in-Aid from the Kyushu Bureau of the Ministry of Economy, Trade and Industry of Japan (No. 17G8009 to Hironobu Yanagie), and a Grant from the Foundation of Kyushu Medical Resource in Japan.

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Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a 10BSH-containing WOW emulsion

Highlights

Abstract

Introduction

Section snippets

Human subject protection

Case presentation

Discussion

Conclusions

Acknowledgments

Radiat.Meas.

Appl. Radiat. Isot.

Int. J. Radiat. Oncol. Biol. Phys.

Biomed. Pharmacother.

Appl. Radiat. Isot.

Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdoloplets containing fine aqueous vesicles of epirubicin

Cancer

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a ¹⁰BSH-containing WOW emulsion