Antoine Leimgruber1, Andreas Möller2, Sarah J Everitt3, Marine Chabrot4, David L Ball5, Ben Solomon6, Michael MacManus5, Rodney J Hicks7. 1. Centre for Molecular Imaging, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Department of Medical Imaging, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 2. QIMR Berghofer Medical Research Institute, Herston Queensland, Australia. 3. Department of Radiation Oncology, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, Victoria, Australia; and. 4. Centre for Molecular Imaging, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. 5. Department of Radiation Oncology, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. 6. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. 7. Centre for Molecular Imaging, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia rod.hicks@petermac.org.
Abstract
UNLABELLED: Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens. METHODS: Sixty patients with non-small cell lung cancer underwent concurrent radical chemoradiotherapy to 60 Gy in 6 wk with either cisplatin/etoposide (C/E, n = 28) weeks 1 and 5 or weekly carboplatin/paclitaxel (C/P, n = 32) regimens. (18)F-FLT and (18)F-FDG PET with CT were performed at baseline, week 2 (day 9 for (18)F-FLT and day 10 for (18)F-FDG PET), and week 4 (day 23 for (18)F-FLT and day 24 for (18)F-FDG PET). Visual and semiquantitative standardized uptake value (SUV) measurements were performed in bone marrow outside the radiotherapy field, liver, spleen, and small bowel. These were correlated to blood counts and smears in a subset of patients. RESULTS: The C/E group exhibited a drop in bone marrow (18)F-FLT uptake at week 2 (median SUVmax [maximum SUV] decrease to 31%, 8.7-6.0, P < 0.001), with recovery at week 4, reflecting the absence of chemotherapy between these times. By contrast, the weekly C/P group showed gradually declining bone marrow uptake (P > 0.05). Spleen uptake in both cohorts decreased at week 2, with intense rebound activity at week 4 (SUVmax week 4 at 58% above baseline: 2.4-3.8, for C/E, respectively, 30% for C/P: 2.7-3.5, P < 0.001). Liver uptake changed little. (18)F-FLT changes preceded neutrophil count reductions. (18)F-FDG uptake in marrow liver and spleen changed much less than (18)F-FLT. CONCLUSION: (18)F-FLT imaging may be used to quantify impairment and recovery of bone marrow by specific chemotherapy regimens and may also enable imaging of organ-specific processes such as spleen activation. (18)F-FLT is superior to (18)F-FDG for this purpose. This technology may support novel treatment planning and monitoring approaches in oncology patients.
UNLABELLED: Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens. METHODS: Sixty patients with non-small cell lung cancer underwent concurrent radical chemoradiotherapy to 60 Gy in 6 wk with either cisplatin/etoposide (C/E, n = 28) weeks 1 and 5 or weekly carboplatin/paclitaxel (C/P, n = 32) regimens. (18)F-FLT and (18)F-FDG PET with CT were performed at baseline, week 2 (day 9 for (18)F-FLT and day 10 for (18)F-FDG PET), and week 4 (day 23 for (18)F-FLT and day 24 for (18)F-FDG PET). Visual and semiquantitative standardized uptake value (SUV) measurements were performed in bone marrow outside the radiotherapy field, liver, spleen, and small bowel. These were correlated to blood counts and smears in a subset of patients. RESULTS: The C/E group exhibited a drop in bone marrow (18)F-FLT uptake at week 2 (median SUVmax [maximum SUV] decrease to 31%, 8.7-6.0, P < 0.001), with recovery at week 4, reflecting the absence of chemotherapy between these times. By contrast, the weekly C/P group showed gradually declining bone marrow uptake (P > 0.05). Spleen uptake in both cohorts decreased at week 2, with intense rebound activity at week 4 (SUVmax week 4 at 58% above baseline: 2.4-3.8, for C/E, respectively, 30% for C/P: 2.7-3.5, P < 0.001). Liver uptake changed little. (18)F-FLT changes preceded neutrophil count reductions. (18)F-FDG uptake in marrow liver and spleen changed much less than (18)F-FLT. CONCLUSION: (18)F-FLT imaging may be used to quantify impairment and recovery of bone marrow by specific chemotherapy regimens and may also enable imaging of organ-specific processes such as spleen activation. (18)F-FLT is superior to (18)F-FDG for this purpose. This technology may support novel treatment planning and monitoring approaches in oncology patients.
Authors: Willem Grootjans; Lioe-Fee de Geus-Oei; Esther G C Troost; Eric P Visser; Wim J G Oyen; Johan Bussink Journal: Nat Rev Clin Oncol Date: 2015-04-28 Impact factor: 66.675
Authors: Jeffrey C Wyss; Ruben Carmona; Roshan A Karunamuni; Jakub Pritz; Carl K Hoh; Loren K Mell Journal: Radiother Oncol Date: 2015-12-07 Impact factor: 6.280
Authors: Shu Wen Wen; Sarah J Everitt; Justin Bedő; Marine Chabrot; David L Ball; Benjamin Solomon; Michael MacManus; Rodney J Hicks; Andreas Möller; Antoine Leimgruber Journal: PLoS One Date: 2015-11-24 Impact factor: 3.240