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

Vilhelmsson Timmermand, Oskar LU orcid ; Ulmert, David ; Evans-Axelsson, Susan ; Pettersson, Kim ; Bjartell, Anders ; Lilja, Hans ; Strand, Sven-Erik LU and Tran, Thuy LU (2014) In EJNMMI Research 4.
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(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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Prostate cancer, Human kallikrein-related peptidase 2, Human kallikrein, gene family, In-111-DTPA-11B6, Molecular imaging
in
EJNMMI Research
volume
4
article number
51
publisher
BioMed Central (BMC)
external identifiers
  • wos:000358051100001
  • pmid:26116115
  • scopus:84930817292
  • pmid:26116115
ISSN
2191-219X
DOI
10.1186/s13550-014-0051-5
language
English
LU publication?
yes
id
f25ae233-c390-438b-b0be-0ff87e697336 (old id 7790969)
date added to LUP
2016-04-01 14:13:14
date last changed
2025-01-03 21:24:08
@article{f25ae233-c390-438b-b0be-0ff87e697336,
  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(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.}},
  author       = {{Vilhelmsson Timmermand, Oskar and Ulmert, David and Evans-Axelsson, Susan and Pettersson, Kim and Bjartell, Anders and Lilja, Hans and Strand, Sven-Erik and Tran, Thuy}},
  issn         = {{2191-219X}},
  keywords     = {{Prostate cancer; Human kallikrein-related peptidase 2; Human kallikrein; gene family; In-111-DTPA-11B6; Molecular imaging}},
  language     = {{eng}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{EJNMMI Research}},
  title        = {{Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a In-111-radiolabelled monoclonal antibody, 11B6}},
  url          = {{http://dx.doi.org/10.1186/s13550-014-0051-5}},
  doi          = {{10.1186/s13550-014-0051-5}},
  volume       = {{4}},
  year         = {{2014}},
}