Preparation and biodistribution of ¹⁸⁸Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (¹⁸⁸Re-folate-CDDP/HSA MNPs) in vivo

Qiu-Sha Tang^1,*, Dao-Zhen Chen^2,*, Wen-Qun Xue², Jing-Ying Xiang², Yong-Chi Gong¹, Li Zhang², Cai-Qin Guo^2
1Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu; ²Central Laboratory, Wuxi Hospital for Maternal and Child Health Care, Affiliated Medical School of Nanjin, Wuxi, Jiangsu, China
^*Authors contributed equally to this work

Background: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide ¹⁸⁸Re-labeled folic acid ligand (¹⁸⁸Re-folate-CDDP/HSA).
Methods: Human serum albumin was labeled with ¹⁸⁸Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of ¹⁸⁸Re-folate-CDDP/HAS magnetic nanoparticles was assessed.
Results: Optimal conditions for ¹⁸⁸Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and ¹⁸⁸ReO₄ eluent (0.1 mL). The rate of ¹⁸⁸Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the ¹⁸⁸Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of ¹⁸⁸Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo.
Conclusion: These results indicate that ¹⁸⁸Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide (¹⁸⁸Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.

Keywords: cisplatin, folic acid, albumin, magnetic nanoparticles, ¹⁸⁸Re, ovarian cancer