title: Comparison of the therapeutic efficacy of 188Rhenium-liposomes and liposomal             doxorubicin in a 4T1 murine orthotopic breast cancer model.
abstract: Liposomal doxorubicin (Lipo-DOX) has been widely and successfully used in chemotherapy for breast cancer patients. Since our previous studies found that 188Rhenium (188Re)-N,N-bis (2-mercaptoethyl)-N',N'-diethy-lethylenediamine (BMEDA)-labeled pegylated liposomes (188Re-liposomes) have radiotherapeutic potential in a colon cancer model, and little information is available to make a comparison of the therapeutic efficacy of internal radiotherapy and chemotherapy, this study evaluates the therapeutic efficacy of 188Re-liposomes and Lipo-DOX, in a 4T1 murine orthotopic breast cancer model. MicroSPECT/CT imaging showed that the highest uptake of 188Re-liposomes was found at 24 h after intravenous administration. The results of a bio-distribution assay also demonstrated that the highest uptake of 188Re-liposomes in a tumor was 3.03±0.29 (%ID/g) at 24 h, and that the highest tumor to muscle ratio was approximately 17 at 48 h. According to measurements of body weight and survival rate, the maximum tolerated doses (MTD) of 188Re-liposomes and Lipo-DOX were 37 MBq and 25 mg/kg, respectively. In a study of therapeutic efficacy, mice with 4T1 orthotopic breast tumors that were treated with 188Re-liposomes (4/5 MTD, 29.6 MBq) or Lipo-DOX (4/5 MTD, 20 mg/kg), showed a significant inhibition of tumor growth. In the small tumor model (50 mm3), the lifespan of 4T1 tumor-bearing mice treated with 188Re-liposomes and Lipo-DOX was increased by 21.7 and 169.6%, respectively, compared to those treated with normal saline. In the large tumor model (300 mm3), the lifespan of the 188Re-liposomes and the Lipo-DOX treated group was also increased by 35.2 and 141.2%, respectively. In this study, it was found that Lipo-DOX is better than 188Re-liposomes, for the treatment of 4T1 breast cancer. A further investigation of combined therapy, in a breast cancer model, using 188Re-liposomes and Lipo-Dox, to determine whether a synergistic effect exists, is ongoing in our laboratory.
authors: Isotope Application Division, Institute of Nuclear Energy Research, No. 1000 Wenhua Road, Chiaan Village, Lungtan, Taoyuan 325, Taiwan, ROC.
authors: Chi-Mou
authors: CM
authors: Liu
authors: Wan-Chi
authors: WC
authors: Lee
authors: Chia-Yu
authors: CY
authors: Yu
authors: Keng-Li
authors: KL
authors: Lan
authors: Chih-Hsien
authors: CH
authors: Chang
authors: Gann
authors: G
authors: Ting
authors: Te-Wei
authors: TW
authors: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous / Q000379:methods; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011868:Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012211:Rhenium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D011868:Radioisotopes; D012211:Rhenium; D004317:Doxorubicin