title: Tumor burden talks in cancer treatment with PEGylated liposomal drugs.
abstract: OBJECTIVE
  PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR) effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model.
  
  
  METHODS
  Empty PEGylated liposomes (NanoX) and those encapsulated with VNB (NanoVNB) were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%). BALB/c mice bearing either small (58.4±8.0 mm(3)) or large (102.4±22.0 mm(3)) C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging) and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment.
  
  
  RESULTS
  The biodistribution study of InVNBL revealed a clear inverse correlation (r (2) = 0.9336) between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug) showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only) and InNanoX (radionuclide only). Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors.
  
  
  CONCLUSIONS
  The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs.
authors.affiliation: Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Hao-Wen
authors.initials: HW
authors.lastname: Kao
authors.forename: Jia-Je
authors.initials: JJ
authors.lastname: Li
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Tseng
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001835:Body Weight; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008081:Liposomes / Q000737:chemistry; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D014055:Tomography, Emission-Computed; D047368:Tumor Burden / Q000187:drug effects*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D011092:Polyethylene Glycols; D014747:Vinblastine; D000077235:Vinorelbine