Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride in a CT1258 based in vivo model of prostate cancer

Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in in-vivo 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 in-vivo 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 (MnCl.sub.2) represent powerful tools for the in-vivo characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl.sub.2 or SPIOs in vitro and used 1 T MRI for tracing labelled cells in-vitro and 7 T MRI for tracking in an in-vivo animal model. Labelling of prostate cancer cells CT1258 was established in-vitro with MnCl.sub.2 and SPIOs. In-vitro detection of labelled cells in an agar phantom was carried out through 1 T MRI while in-vivo 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. MnCl.sub.2in-vitro labelling resulted in no significant metabolic effects on proliferation and cell vitality. In-vitro detection-limit accounted 10.sup.5 cells for MnCl.sub.2 as well as for SPIOs labelling. In-vivo 7 T MRI scans allowed detection of 10.sup.3 and 10.sup.4 cells. In-vivo MnCl.sub.2 labelled cells were detectable from days 4-16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl.sub.2 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. To the best of our knowledge, this is the first study reporting direct in-vitro MnCl.sub.2 labelling and 7 T based in-vivo MRI tracing of cancer cells in a model of prostate cancer. MnCl.sub.2 labelling was found to be suitable for in-vivo tracing allowing long detection periods. The labelled cells kept their highly tumourigenic potential in-vivo. Tumour volume develop