Primary research

Multicellular Tumour Spheroid as a model for evaluation of [¹⁸F]FDG as biomarker for breast cancer treatment monitoring

Azita Monazzam^1,4 , Pasha Razifar^2,4 , Martin Simonsson¹ , Fredrik Qvarnström¹ , Raymond Josephsson^5,6 , Carl Blomqvist¹ , Bengt Långström⁴ and Mats Bergström^3,4,5

¹  Department of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala, Sweden

²  Uppsala University, Centre for Image Analysis, Lägerhyddsvägen 3, SE-752 37 Uppsala, Sweden

³  Department of Pharmaceutical Biosciences, Uppsala University, Sweden

⁴  Uppsala Imanet AB (PET Center), BOX 967, Sweden

⁵  Novartis Pharma AG, Clinical Imaging, CH-4002 Basel, Switzerland

⁶  Department of medical Science, The Academic Hospital, S-751 85 Uppsala, Sweden

author email corresponding author email

Cancer Cell International 2006, 6:6doi:10.1186/1475-2867-6-6

Published:	23 March 2006

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.