Therapeutic efficacy and microSPECT/CT imaging of 188Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model.
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.
Chang
Ya-Jen
YJ
Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC.
Chang
Chih-Hsien
CH
Yu
Chia-Yu
CY
Chang
Tsui-Jung
TJ
Chen
Liang-Cheng
LC
Chen
Min-Hua
MH
Lee
Te-Wei
TW
Ting
Gann
G
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
D011868:Radioisotopes; D012211:Rhenium; D004317:Doxorubicin