Alexandr Kristian1,2,3, Jon Erik Holtedahl4, Turid Torheim5, Cecilia Futsaether5, Eivor Hernes6, Olav Engebraaten1,2,3,7, Gunhild M Mælandsmo1,2,8, Eirik Malinen9,10. 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.
PURPOSE: Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancerpatients. 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.
Authors: Alexandr Kristian; Line B Nilsen; Kathrine Røe; Mona-Elisabeth Revheim; Olav Engebråten; Gunhild M Mælandsmo; Ruth Holm; Eirik Malinen; Therese Seierstad Journal: Nucl Med Mol Imaging Date: 2013-06-21
Authors: Kathrine Røe; Thomas B Aleksandersen; Alexandr Kristian; Line B Nilsen; Therese Seierstad; Hong Qu; Anne H Ree; Dag R Olsen; Eirik Malinen Journal: Acta Oncol Date: 2010-10 Impact factor: 4.089
Authors: C M Perou; T Sørlie; M B Eisen; M van de Rijn; S S Jeffrey; C A Rees; J R Pollack; D T Ross; H Johnsen; L A Akslen; O Fluge; A Pergamenschikov; C Williams; S X Zhu; P E Lønning; A L Børresen-Dale; P O Brown; D Botstein Journal: Nature Date: 2000-08-17 Impact factor: 49.962
Authors: Peter Lind; Isabel Igerc; Thomas Beyer; Peter Reinprecht; Klaus Hausegger Journal: Eur J Nucl Med Mol Imaging Date: 2004-04-15 Impact factor: 9.236
Authors: Alexandr Kristian; Mona Elisabeth Revheim; Hong Qu; Gunhild M Mælandsmo; Olav Engebråten; Therese Seierstad; Eirik Malinen Journal: Acta Oncol Date: 2013-08-29 Impact factor: 4.089