title: Effect of Platinum-Based Chemoradiotherapy on Cellular Proliferation in Bone Marrow and Spleen, Estimated by (18)F-FLT PET/CT in Patients with Locally Advanced Non-Small Cell Lung Cancer.
abstract: 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.
  
  
  CONCLUSIONS
  (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.affiliation: 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.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leimgruber
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Möller
authors.affiliation: 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.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Everitt
authors.affiliation: Centre for Molecular Imaging, Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Marine
authors.initials: M
authors.lastname: Chabrot
authors.affiliation: 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.
authors.forename: David L
authors.initials: DL
authors.lastname: Ball
authors.affiliation: The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Solomon
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: MacManus
authors.affiliation: 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.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000009:adverse effects*; D015224:Dideoxynucleosides; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D009928:Organ Specificity; D010984:Platinum / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D014057:Tomography, X-Ray Computed
chemical_list: D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; D010984:Platinum; D005947:Glucose; C002854:alovudine
keywords: 18F-FLT; bone marrow; chemo-toxicity; hematopoiesis; spleen