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Mol Imaging Biol. 2017 Apr;19(2):271-279. doi: 10.1007/s11307-016-0998-x.

Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts.

Author information

1
Department of Tumor Biology, Oslo University Hospital, Oslo, Norway.
2
K.G. Jebsen Center for Breast Cancer Research, University of Oslo, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
4
The Intervention Centre, Oslo University Hospital, Oslo, Norway.
5
Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.
6
Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
7
Department of Oncology, Oslo University Hospital, Oslo, Norway.
8
Department of Pharmacy, University of Tromsø, Tromsø, Norway.
9
Department of Physics, University of Oslo, Oslo, Norway. eirik.malinen@fys.uio.no.
10
Department of Medical Physics, Oslo University Hospital, Oslo, Norway. eirik.malinen@fys.uio.no.

Abstract

PURPOSE:

Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens.

PROCEDURES:

Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [18F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUVE and SUVL, respectively); the rate constants k 1, k 2, and k 3, and the intravascular fraction v B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response.

RESULTS:

Treatment responders had significantly larger perfusion-related parameters (k 1 and k 2) and lower metabolism-related parameter (k 3) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k 1 and k 2 at day 10 and changes in k 3 explained most of the variability in response to therapy, whereas SUVL and particularly SUVE were of lesser importance.

CONCLUSIONS:

Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [18F]FDG uptake such as SUVE and SUVL apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.

KEYWORDS:

2-deoxy-2-[18F]fluoro-D-glucose; Breast cancer; Chemotherapy; Partial least-squares regression; Pharmacokinetic analysis; Positron emission tomography

PMID:
27541026
DOI:
10.1007/s11307-016-0998-x
[Indexed for MEDLINE]

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