Application of the multicellular tumour spheroid model to screen PET tracers for analysis of early response of chemotherapy in breast cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Monazzam
Azita
A
Institute of Oncology, Institute of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. azita.monazzam@uppsala.imanet.se
Josephsson
Raymond
R
Blomqvist
Carl
C
Carlsson
Jörgen
J
Långström
Bengt
B
Bergström
Mats
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D000068877:Imatinib Mesylate; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008954:Models, Biological; D017239:Paclitaxel / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000008:administration & dosage; D019275:Radiopharmaceuticals; D018874:Spheroids, Cellular / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001549:Benzamides; D019394:Ki-67 Antigen; D010879:Piperazines; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D043823:Taxoids; D013629:Tamoxifen; D000077143:Docetaxel; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D017239:Paclitaxel