title: Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer.
abstract: BACKGROUND
  The kinetics of the bone marrow uptake of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer.
  
  
  METHODS
  Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K(FLT)) and the Patlak constant (K(Patlak)) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined.
  
  
  RESULTS
  There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08+/-0.66, K(FLT)=0.045+/-0.016 min(-1) and K(Patlak)=0.039+/-0.013 min(-1). After treatment, these values were SUV=0.74+/-0.19, K(FLT)=0.011+/-0.005 min(-1) and K(Patlak)=0.005+/-0.002 min(-1). Compartmental analysis revealed a significant drop in k(3) in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease.
  
  
  CONCLUSIONS
  There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. yusuf-menda@uiowa.edu
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Menda
authors.forename: Laura L Boles
authors.initials: LL
authors.lastname: Ponto
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Dornfeld
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Tewson
authors.forename: G Leonard
authors.initials: GL
authors.lastname: Watkins
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Carryn
authors.initials: C
authors.lastname: Anderson
authors.forename: Sarah
authors.initials: S
authors.lastname: McGuire
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schultz
authors.forename: John J
authors.initials: JJ
authors.lastname: Sunderland
authors.forename: Michael M
authors.initials: MM
authors.lastname: Graham
authors.forename: John M
authors.initials: JM
authors.lastname: Buatti
mesh_terms: D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013997:Time Factors
chemical_list: D015224:Dideoxynucleosides; C002854:alovudine
references.citation: Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1098-104
references.pmid: 19386444
references.citation: Blood. 1966 Sep;28(3):398-415
references.pmid: 5918471
references.citation: J Nucl Med. 2009 Jul;50(7):1028-35
references.pmid: 19525472
references.citation: AJR Am J Roentgenol. 1990 Apr;154(4):745-50
references.pmid: 2107669
references.citation: J Nucl Med. 2004 Apr;45(4):695-700
references.pmid: 15073267
references.citation: Exp Cell Res. 1967 Nov;48(2):473-83
references.pmid: 6082324
references.citation: J Nucl Med. 2002 Sep;43(9):1210-7
references.pmid: 12215561
references.citation: Eur J Nucl Med Mol Imaging. 2005 Nov;32(11):1269-75
references.pmid: 15991018
references.citation: Cancer. 1973 Sep;32(3):699-711
references.pmid: 4726969
references.citation: Eur J Nucl Med Mol Imaging. 2007 Jul;34(7):1003-11
references.pmid: 17295039
references.citation: Cell Prolif. 2002 Apr;35(2):69-81
references.pmid: 11952642
references.citation: Phys Med Biol. 1961 Jan;5:255-8
references.pmid: 13726497
references.citation: Cell Growth Differ. 1998 Nov;9(11):887-96
references.pmid: 9831241
references.citation: J Nucl Med. 2008 Nov;49(11):1756-62
references.pmid: 18927328
references.citation: J Nucl Med. 2000 Dec;41(12):2026-35
references.pmid: 11138688
references.citation: Am J Roentgenol Radium Ther Nucl Med. 1966 Jan;96(1):183-90
references.pmid: 5900876
references.citation: J Cereb Blood Flow Metab. 1983 Mar;3(1):1-7
references.pmid: 6822610
references.citation: Phys Med Biol. 1968 Jan;13(1):1-14
references.pmid: 4868275
references.citation: J Nucl Med. 2005 Feb;46(2):371-80
references.pmid: 15695799
references.citation: Nat Med. 1998 Nov;4(11):1334-6
references.pmid: 9809561