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Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a In-111-radiolabelled monoclonal antibody, 11B6

Author:
  • Oskar Vilhelmsson Timmermand
  • David Ulmert
  • Susan Evans-Axelsson
  • Kim Pettersson
  • Anders Bjartell
  • Hans Lilja
  • Sven-Erik Strand
  • Thuy Tran
Publishing year: 2014
Language: English
Publication/Series: EJNMMI Research
Volume: 4
Document type: Journal article
Publisher: BioMed Central

Abstract english

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 IgG(1) monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of In-111-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer. Methods: 11B6 was radiolabelled with In-111 through CHX-A"-DTPA chelation. In vivo biodistribution and uptake of In-111-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 In-111-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 In-111-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.

Keywords

  • Radiology, Nuclear Medicine and Medical Imaging
  • Prostate cancer
  • Human kallikrein-related peptidase 2
  • Human kallikrein
  • gene family
  • In-111-DTPA-11B6
  • Molecular imaging

Other

Published
  • ISSN: 2191-219X
Sven-Erik Strand
E-mail: sven-erik [dot] strand [at] med [dot] lu [dot] se

Project manager

Systemic Radiation Therapy Group

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Professor emeritus

Medical Radiation Physics, Lund

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