Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl₂) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based <it>in vivo</it> model of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in <it>in-vivo</it> animal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI) based <it>in-vivo</it> characterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs) and manganese chloride (MnCl₂) represent powerful tools for the <it>in-vivo</it> characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl₂ or SPIOs <it>in vitro</it> and used 1 T MRI for tracing labelled cells <it>in-vitro</it> and 7 T MRI for tracking in an <it>in-vivo</it> animal model.</p> <p>Methods</p> <p>Labelling of prostate cancer cells CT1258 was established <it>in-vitro</it> with MnCl₂ and SPIOs. <it>In-vitro</it> detection of labelled cells in an agar phantom was carried out through 1 T MRI while <it>in-vivo</it> detection was performed using 7 T MRI after subcutaneous (s.c.) injection of labelled cells into NOD-Scid mice (n = 20). The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination.</p> <p>Results</p> <p>MnCl₂<it>in-vitro</it> labelling resulted in no significant metabolic effects on proliferation and cell vitality. <it>In-vitro</it> detection-limit accounted 10⁵ cells for MnCl₂ as well as for SPIOs labelling. <it>In-vivo</it> 7 T MRI scans allowed detection of 10³ and 10⁴ cells. <it>In-vivo</it> MnCl₂ labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl₂ labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size development and disease progression. Histological analysis of the induced tumour masses demonstrated characteristic morphologies of prostate adenocarcinoma.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first study reporting direct <it>in-vitro</it> MnCl₂ labelling and 7 T based <it>in-vivo</it> MRI tracing of cancer cells in a model of prostate cancer. MnCl₂ labelling was found to be suitable for <it>in-vivo</it> tracing allowing long detection periods. The labelled cells kept their highly tumourigenic potential <it>in-vivo.</it> Tumour volume development was visualised prior to manual palpation allowing tumour characterisation in early stages of the disease.</p