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1.  Application of the multicellular tumour spheroid model to screen PET tracers for analysis of early response of chemotherapy in breast cancer 
Positron emission tomography (PET) is suggested for early monitoring of treatment response, assuming that effective anticancer treatment induces metabolic changes that precede morphology alterations and changes in growth. The aim of this study was to introduce multicellular tumour spheroids (MTS) to study the effect of anticancer drugs and suggest an appropriate PET tracer for further studies.
MTS of the breast cancer cell line MCF7 were exposed to doxorubicin, paclitaxel, docetaxel, tamoxifen or imatinib for 7 days for growth pattern studies and for 3 or 5 days for PET tracer studies. The effect on growth was computed using the semi-automated size determination method (SASDM). The effect on the uptake of PET tracers [18F]3'-deoxy-3'-fluorothymidine (FLT), [1-11C]acetate (ACE), [11C]choline (CHO), [11C]methionine (MET), and 2-[18F]fluoro-2-deoxyglucose (FDG) was calculated in form of uptake/viable volume of the MTS at the end of the drug exposures, and finally the uptake was related to effects on growth rate.
The drugs paclitaxel, docetaxel and doxorubicin gave severe growth inhibition, which correlated well with inhibition of the FLT uptake. FLT had, compared with ACE, CHO, MET and FDG, higher sensitivity in monitoring the therapy effects.
SASDM provides an effective, user-friendly, time-saving and accurate method to record the growth pattern of the MTS, and also to calculate the effect of the drug on PET tracer uptake. This study demonstrate the use of MTS and SASDM in combination with PET tracers as a promising approach to probe and select PET tracer for treatment monitoring of anticancer drugs and that can hopefully be applied for optimisation in breast cancer treatment.
PMCID: PMC2206720  PMID: 17659092
2.  Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring 
In order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS) without and with treatment with five routinely used chemotherapy agents in breast cancer.
The response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment.
The effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease) than in MCF-7 (up to 25% decrease).
Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25%) than in BT474 MTSs.
Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM.
No effect of Imatinib was observed.
MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur.
The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response.
In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.
PMCID: PMC1459213  PMID: 16556298

Results 1-2 (2)