We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preclinical evaluation of [<sup>111</sup>In]MICA-401, an activity-based probe for SPECT imaging of in vivo uPA activity.
- Authors
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
- 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 (111In)-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 111In ([111In]MICA-401), together with its inactive, hydrolysed form ([111In]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 [111In]MICA-402 showed almost complete clearance 95 h post injection. The ex vivo biodistribution and SPECT data with [111In]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.
- Publication
Contrast Media & Molecular Imaging, 2016, Vol 11, Issue 6, p448
- ISSN
1555-4309
- Publication type
Article
- DOI
10.1002/cmmi.1706