title: Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a (111)In-radiolabelled monoclonal antibody, 11B6.
abstract: BACKGROUND
  Prostate cancer is a leading cause of death in the male population of the western world. Human kallikrein-related peptidase 2 (hK2) is abundantly expressed in malignant prostatic tissue, and its gene, KLK2, is regulated by the androgen receptor. 11B6 is a murine IgG1 monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of (111)In-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer.
  
  
  METHODS
  11B6 was radiolabelled with (111)In through CHX-A″-DTPA chelation. In vivo biodistribution and uptake of (111)In-DTPA-11B6 were measured until 168 h post-injection in NMRI nude mice bearing subcutaneous LNCaP xenografts. The binding specificity to hK2 was evaluated by both in vivo competitive binding assays with excess non-labelled 11B6 and hK2-negative DU145 xenografts. SPECT/CT imaging of subcutaneous and intra-tibial LNCaP xenografts was used to visualize the tumours.
  
  
  RESULTS
  Tumour uptake of (111)In-DTPA-11B6 in LNCaP xenografts was 19% ± 0.78%IA/g at 48 h, giving a tumour-to-blood ratio of 1.6, which increases to 2.4 at 1 week post-injection. Accumulation was low in other organs except for the salivary glands, which is probably the result of cross-reactivity with mouse kallikreins. Significantly lower tumour accumulation was observed in competitive assays and DU145 xenografts. SPECT/CT imaging could clearly visualize the subcutaneous and intra-tibial LNCaP xenografts.
  
  
  CONCLUSIONS
  Our study demonstrates the potential of (111)In-DTPA-11B6 for the detection of metastatic prostate cancer and monitoring anti-androgen therapy, as it exhibits an increased uptake and accumulation in viable tumour when compared to normal tissue. A humanised version of the 11B6 monoclonal antibody is currently under evaluation.
authors.affiliation: Department of Medical Radiation Physics, Lund University, Barngatan 2:1, S-211 85, Lund, Sweden, oskar.vilhelmsson_timmermand@med.lu.se.
authors.forename: Oskar Vilhelmsson
authors.initials: OV
authors.lastname: Timmermand
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.forename: Susan
authors.initials: S
authors.lastname: Evans-Axelsson
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Strand
authors.forename: Thuy A
authors.initials: TA
authors.lastname: Tran