title: Preliminary radioimmunoimaging and biodistribution of ¹³¹iodine-labeled single-chain antibody fragment against progastrin-releasing peptide(₃₁₋₉₈) in small cell lung cancer xenografts.
abstract: BACKGROUND
  Monoclonal antibodies (mAbs) such as DD3, raised against progastrin-releasing peptide(31-98) (ProGRP (31-98)) antigen, have been used to target small cell lung cancer (SCLC). However, as an intact mAb, DD3 is cleared slowly from the body, with an optimal radioimmunoimaging time of 72 hours. More recently, a single-chain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research. Thereby, it potentially increases the radioimmunoimaging efficacy. However, there have been few studies with this antibody fragment. The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of (131)I-anti-ProGRP(31-98) scFv in nude mice bearing SCLC xenografts.
  
  
  METHODS
  Anti-ProGRP(31-98) scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry. (131)I-anti-ProGRP(31-98) scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram (%ID/g) in various organs was calculated. Similarly, the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated. After injection of (131)I-anti-ProGRP(31-98) scFv, treated mice were imaged at 1, 24, and 30 hours. Then the tumor/base ratios were calculated.
  
  
  RESULTS
  ProGRP was highly expressed in NCI-H446 cells and xenograft tissue. The metabolism of (131)I-anti-ProGRP(31-98) scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes, respectively. The %ID/g of (131)I-anti-ProGRP(31-98) scFv in xenografts was much higher than in healthy tissues at 12 hours after injection, reaching a maximum of (5.38±0.92) %ID/g at 24 hours. Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours, with 24 hours proving optimal.
  
  
  CONCLUSIONS
  (131)I-anti-ProGRP(31-98) scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance, indicating that it could be a promising agent for SCLC radioimmunoimaging.
authors.affiliation: Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China. Email: liuzengli@126.com.
authors.forename: Zengli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiology and Nuclear Medicine, China Institute for Radiation Protection, Taiyuan, Shanxi 030006, China. Email: xiaolin0824@sohu.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000276:immunology*; D016719:Radioimmunodetection / Q000379:methods*; D011994:Recombinant Proteins / Q000276:immunology; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007128:Immunoglobulin Fragments; D010446:Peptide Fragments; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98)