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 |
| DOI/URL: | |
| Notes: | Export Date: 2 July 2015 -- Source: Scopus |
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