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- Document type:
- Journal Article; Article
- Author(s):
- Vangestel, Christel; Thomae, David; Van Soom, Jeroen; Ides, Johan; Wyffels, Leonie; Pauwels, Patrick; Stroobants, Sigrid; Van der Veken, Pieter; Magdolen, Viktor; Joossens, Jurgen; Augustyns, Koen; Staelens, Steven
- Title:
- Preclinical evaluation of [(111) In]MICA-401, an activity-based probe for SPECT imaging of in vivo uPA activity.
- Abstract:
- Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 are key players in cancer invasion and metastasis. Both uPA and PAI-1 have been described as prognostic biomarkers; however, non-invasive methods measuring uPA activity are lacking. We developed an indium-111 ((111) In)-labelled activity-based probe to image uPA activity in vivo by single photon emission computed tomography (SPECT). A DOTA-conjugated uPA inhibitor was synthesized and radiolabelled with (111) In ([(111) In]MICA-401), together with its inactive, hydrolysed form ([(111) In]MICA-402). A biodistribution study was performed in mice (healthy and tumour-bearing), and tumour-targeting properties were evaluated in two different cancer xenografts (MDA-MB-231 and HT29) with respectively high and low levels of uPA expression in vitro, with either the active or hydrolysed radiotracer. MicroSPECT was performed 95 h post injection followed by ex vivo biodistribution. Tumour uptake was correlated with human and murine uPA expression determined by ELISA and immunohistochemistry (IHC). Biodistribution data with the hydrolysed probe [(111) In]MICA-402 showed almost complete clearance 95 h post injection. The ex vivo biodistribution and SPECT data with [(111) In]MICA-401 demonstrated similar tumour uptakes in the two models: ex vivo 5.68 ± 1.41%ID/g versus 5.43 ± 1.29%ID/g and in vivo 4.33 ± 0.80 versus 4.86 ± 1.18 for MDA-MB-231 and HT-29 respectively. Human uPA ELISA and IHC showed significantly higher uPA expression in the MDA-MB-231 tumours, while mouse uPA staining revealed similar staining intensities of the two tumours. Our data demonstrate non-invasive imaging of uPA activity in vivo, although the moderate tumour uptake and hence potential clinical translation of the radiotracer warrants further investigation. Copyright © 2016 John Wiley & Sons, Ltd.
- Journal title abbreviation:
- Contrast Media Mol Imaging
- Year:
- 2016
- Journal volume:
- 11
- Journal issue:
- 6
- Pages contribution:
- 448-458
- Language:
- eng
- Fulltext / DOI:
- doi:10.1002/cmmi.1706
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/27558262
- Print-ISSN:
- 1555-4309
- TUM Institution:
- Frauenklinik und Poliklinik
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