Comparative Therapeutic Efficacy of Rhenium-188 Radiolabeled-Liposome and 5-Fluorouracil in LS-174T Human Colon Carcinoma Solid Tumor Xenografts

Abstract

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p<0.05) was significantly better than those of 5-FU (48.25 days; p>0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer&nbsp;xenograft and modulates 188Re-liposome pharmacokinetics

“…13 Re-liposome has a comparative therapeutic efficacy with chemotherapeutic drug 5-FU in colon carcinoma ascites, we found that 188 Re-liposome possesses a better therapeutic efficacy in both lung-metastatic and solid-tumor animal models. 18,[20][21][22] No documents using 188…”

Nanotargeted Radiopharmaceuticals for Nuclear Imaging and Radiotherapy

“…23,33,35,54,71 The radionuclide after-loading method has provided higher labeling efficiencies (>90%) and the greatest in vivo stability for 99m Tc, 111 In and 67 Ga radionuclides for nuclear imaging 23,24,27,35,59,[84][85][86] as well as 186 Re and 188 Re radionuclides for radiotherapy. 72,[87][88][89][90][91][92] This kind of approach is also useful in preparing polymeric NP, lutetium-177-loaded poly(D,L-lactide-co-glycolide) (PLGA) NPs are formulated by simply incubation of pre-formulated blank PLGA 50:50 or 75:25 NPs by incubating with 177 Lu-DOTA-Tyr 3 -octreotate (DOTATATE), although the percentage of encapsulation was about 77%. 93 In the second approach, the radionuclides are bounded to a lipid chelator, inserted and loaded into the liposomal bilayer or radionuclide chelators are covalently attached to the surface of the liposomes or NPs after forming.…”

“…111 The SPECT/CT imaging of 188 Re-liposome targeting on LS-174T human colorectal tumor bearing nude mouse model were also proved recently. 89 SPECT/CT imaging of passive tumor targeting, pharmacokinetics and excretion of 188 Re-liposomes were studied in C26 murine colon carcinoma solid tumor-bearing mice, C26 colon carcinoma ascites-bearing mice, C26 colon carcinoma lung metastatic mice model and LS-174T human colon carcinoma solid tumor-bearing mice. Elimination half-lives (T 1/2λz ) of of PEGylated nanoliposome therapeutics loaded with 188 Re.…”

“…The 188 Re-liposome was mostly excreted via feces suggesting the importance of hepatobiliary excretion for these radiolabeled NPs. 87,111,[89][90][91][92] Gamma and SPECT imaging of 131 I and 64 Cu radiolabeled polymeric NPs were studied. 45,46 PET , SPECT/magnetic resonance imaging (MRI) dual-modality and SPECT/MRI/optical trimodality imaging of tumor targeting of 99m Tc-, 64 Cu-and 68 Ga-radiolabeled IO NPs were demonstrated.…”

Application of liposomes in drug development &ndash; focus on gastroenterological targets

“…[93][94][95] Rhenium-188 ((188)Re) labeled PEGylated liposomes carrying anticancer drugs showed the potential benefits of tumor specific drug accumulation and cancer growth inhibition. [96][97][98][99] PEGylated liposomes encapsulating (111)Re and vinorelbine was as effective as PEG liposomal (188)Re and doxorubicin for radiochemotherapy of CRC models.…”