131I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization

Qiufang Liu; Yuyi Qian; Panli Li; Sihang Zhang; Jianjun Liu; Xiaoguang Sun; Michael Fulham; Dagan Feng; Gang Huang; Wei Lu; Shaoli Song

doi:10.7150/thno.21491

¹³¹I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization

Theranostics. 2018 Jan 1;8(3):785-799. doi: 10.7150/thno.21491. eCollection 2018.

Authors

Qiufang Liu^{1

2

3}, Yuyi Qian⁴, Panli Li^{1

2

3}, Sihang Zhang⁴, Jianjun Liu^{1

3}, Xiaoguang Sun^{1

3}, Michael Fulham^{2

5

6}, Dagan Feng^{2

6}, Gang Huang^{1

2

7

3}, Wei Lu^{4

8}, Shaoli Song^{1

2

3}

Affiliations

¹ Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² SJTU-USYD Joint Research Alliance for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Institute of Clinical Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.
⁵ Department of Molecular Imaging, Royal Prince Alfred Hospital, Australia and Sydney Medical School, University of Sydney, Sydney, Australia.
⁶ Biomedical and Multimedia Information Technology Research Group, School of Information Technologies, University of Sydney, Sydney, Australia.
⁷ Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China.
⁸ Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, Rhode Island, United States.

Abstract

Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 (¹³¹I) to produce ¹³¹I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of ¹³¹I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of ¹³¹I-HCuSNPs-MS-PTX, ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of ¹³¹I-HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by ¹³¹I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion: Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with ¹³¹I-HCuSNPs-MS-PTX for the treatment of liver tumors.

Keywords: 131I-hollow copper sulfide nanoparticles-microsphere-paclitaxel (131I-HCuSNPs-MS-PTX); embolization.; multifunctional; positron emission tomography/computed tomography (PET/CT).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / therapeutic use
Copper / chemistry
Embolization, Therapeutic / methods*
Hepatic Artery / diagnostic imaging
Iodine Radioisotopes / chemistry
Liver Neoplasms / diagnostic imaging*
Liver Neoplasms / therapy
Male
Microspheres*
Nanoparticles / chemistry*
Paclitaxel / administration & dosage
Paclitaxel / therapeutic use
Photoacoustic Techniques / methods
Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
Positron Emission Tomography Computed Tomography / methods
Rats
Rats, Sprague-Dawley
Sulfides / chemistry
Theranostic Nanomedicine / methods*
Tomography, Emission-Computed, Single-Photon / methods

Substances

Antineoplastic Agents
Iodine Radioisotopes
Sulfides
Polylactic Acid-Polyglycolic Acid Copolymer
cuprous sulfide
Copper
Paclitaxel