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

Authors: Timmermand, O. V.; Ulmert, D.; Evans-Axelsson, S.; Pettersson, K.; Bjartell, A.; Lilja, H.; Strand, S. E.; Tran, T. A.
Article Title: Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a 111In-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 IgG<inf>1</inf> monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of 111In-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer. Methods: 11B6 was radiolabelled with 111In through CHX-A″-DTPA chelation. In vivo biodistribution and uptake of 111In-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 111In-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 111In-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. © 2014, Vilhelmsson Timmermand et al.; licensee Springer.
Keywords: molecular imaging; prostate cancer; human kallikrein-related peptidase 2; 111in-dtpa-11b6; human kallikrein gene family
Journal Title: EJNMMI Research
Volume: 4
ISSN: 2191-219X
Publisher: Springer  
Date Published: 2014-09-19
Start Page: 51
Language: English
DOI: 10.1186/s13550-014-0051-5
PROVIDER: scopus
PMCID: PMC4452661
PUBMED: 26116115
Notes: Export Date: 2 July 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Hans Gosta Lilja
    307 Lilja
  2. Hans David Staffan Ulmert
    51 Ulmert