title: Therapeutic efficacy and microSPECT/CT imaging of 188Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model.
abstract: Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ((188)Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of (188)Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of (188)Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of (188)Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of (188)Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of (188)Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of (188)Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome and the synergistic effect of the combination radiochemotherapeutics of (188)Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of nanoliposome radiochemotherapeutics for adjuvant cancer treatment on oncology applications.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC.
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Yu
authors.forename: Tsui-Jung
authors.initials: TJ
authors.lastname: Chang
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Chen
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Chen
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
mesh_terms: D000818:Animals; D001345:Autoradiography; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004355:Drug Stability; D004358:Drug Therapy; D007275:Injections, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D011868:Radioisotopes / Q000737:chemistry*; D011878:Radiotherapy; D012211:Rhenium / Q000737:chemistry*; D016019:Survival Analysis; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D055114:X-Ray Microtomography
chemical_list: D011868:Radioisotopes; D012211:Rhenium; D004317:Doxorubicin