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Background  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 2 ) represent powerful tools for the  in-vivo  characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl 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.    Methods  Labelling of prostate cancer cells CT1258 was established  in-vitro  with MnCl 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.    Results  MnCl 2  in-vitro  labelling resulted in no significant metabolic effects on proliferation and cell vitality.  In-vitro  detection-limit accounted 10 5  cells for MnCl 2  as well as for SPIOs labelling.  In-vivo  7 T MRI scans allowed detection of 10 3  and 10 4  cells.  In-vivo  MnCl 2  labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl 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.    Conclusions  To the best of our knowledge, this is the first study reporting direct  in-vitro  MnCl 2  labelling and 7 T based  in-vivo  MRI tracing of cancer cells in a model of prostate cancer. MnCl 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 development was visualised prior to manual palpation allowing tumour characterisation in early stages of the disease.

bmc cancer

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