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

International journal of nanomedicine (2011-12-14)
Qiu-Sha Tang, Dao-Zhen Chen, Wen-Qun Xue, Jing-Ying Xiang, Yong-Chi Gong, Li Zhang, Cai-Qin Guo
ABSTRACT

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 (188)Re-labeled folic acid ligand ((188)Re-folate-CDDP/HSA). Human serum albumin was labeled with (188)Re 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 (188)Re-folate-CDDP/HAS magnetic nanoparticles was assessed. Optimal conditions for (188)Re-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 (188)ReO(4) eluent (0.1 mL). The rate of (188)Re-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 (188)Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of (188)Re-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. These results indicate that (188)Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide ((188)Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tin(II) chloride, reagent grade, 98%
Sigma-Aldrich
Tin(II) chloride dihydrate, ACS reagent, 98%
Sigma-Aldrich
Tin(II) chloride dihydrate, reagent grade, 98%
Sigma-Aldrich
Tin(II) chloride, anhydrous, powder, ≥99.99% trace metals basis
Sigma-Aldrich
Tin(II) chloride dihydrate, ≥99.995% trace metals basis
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Tin(II) chloride dihydrate, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Tin(II) chloride, ≥99.99% trace metals basis
Supelco
Tin(II) chloride dihydrate, suitable for AAS
Sigma-Aldrich
Tin(II) chloride dihydrate, ≥99.99% trace metals basis