title: Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: clinical phase I/II trials.
abstract: OBJECTIVE
  HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab'2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials.
  
  
  METHODS
  In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints.
  
  
  RESULTS
  No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019).
  
  
  CONCLUSIONS
  Iodine (131I) metuximab injection is safe and active for HCC patients.
authors.affiliation: Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Mi
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Xing
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Bian
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Jiang
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
authors.forename: Ai-Rong
authors.initials: AR
authors.lastname: Qian
authors.forename: Si-He
authors.initials: SH
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.forename: Zhen-Biao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Nan
authors.initials: N
authors.lastname: Leng
authors.forename: Ting-Shu
authors.initials: TS
authors.lastname: Mo
authors.forename: An-Ren
authors.initials: AR
authors.lastname: Kuang
authors.forename: Tian-Zhi
authors.initials: TZ
authors.lastname: Tan
authors.forename: Yun-Chun
authors.initials: YC
authors.lastname: Li
authors.forename: De-Rong
authors.initials: DR
authors.lastname: Liang
authors.forename: Wu-Sheng
authors.initials: WS
authors.lastname: Lu
authors.forename: Jia
authors.initials: J
authors.lastname: Miao
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Xu
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Nan
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Qing-Guang
authors.initials: QG
authors.lastname: Liu
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007457:Iodine Radioisotopes; C511207:metuximab; D051926:Basigin