title: Spatiotemporal stability of Cu-ATSM and FLT positron emission tomography distributions during radiation therapy.
abstract: OBJECTIVE
  In dose painting, in which functional imaging is used to define biological targets for radiation therapy dose escalation, changes in spatial distributions of biological properties during treatment can compromise the quality of therapy. The goal of this study was to assess the spatiotemporal stability of 2 potential dose painting targets--hypoxia and proliferation--in canine tumors during radiation therapy.
  
  
  METHODS
  Twenty-two canine patients with sinonasal tumors (14 carcinoma and 8 sarcoma) were imaged before hypofractionated radiation therapy with copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) for hypoxia and 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET/CT for proliferation. The FLT scans were repeated after 2 fractions and the Cu-ATSM scans after 3 fractions. Midtreatment PET/CT images were deformably registered to pretreatment PET/CT images. Voxel-based Spearman correlation coefficients quantified the spatial stability of Cu-ATSM and FLT uptake distributions between pretreatment and midtreatment scans. Paired t tests determined significant differences between the patients' respective Cu-ATSM and FLT correlations coefficients. Standardized uptake value measures were also compared between pretreatment and midtreatment scans by use of paired t tests.
  
  
  RESULTS
  Spatial distributions of Cu-ATSM and FLT uptake were stable through midtreatment for both sarcomas and carcinomas: the population mean ± standard deviation in Spearman correlation coefficient was 0.88 ± 0.07 for Cu-ATSM and 0.79 ± 0.13 for FLT. The patients' Cu-ATSM correlation coefficients were significantly higher than their respective FLT correlation coefficients (P=.001). Changes in Cu-ATSM SUV measures from pretreatment to midtreatment were histology dependent: carcinomas experienced significant decreases in Cu-ATSM uptake (P<.05), whereas sarcomas did not (P>.20). Both histologies experienced significant decreases in FLT uptake (P<.05).
  
  
  CONCLUSIONS
  Spatial distributions of Cu-ATSM were very stable after a few fractions of radiation therapy. FLT spatial distributions were generally stable early in therapy, although they were significantly less stable than Cu-ATSM distributions. Canine tumors had significantly lower proliferative activity at midtreatment than at pretreatment, and they experienced histology-dependent changes in Cu-ATSM uptake.
authors.affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Bradshaw
authors.affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors.forename: Stephen
authors.initials: S
authors.lastname: Yip
authors.affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors.forename: Ngoneh
authors.initials: N
authors.lastname: Jallow
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Forrest
authors.affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. Electronic address: rjeraj@wisc.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Jeraj
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy / Q000662:veterinary; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy / Q000662:veterinary; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002813:Chondrosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy / Q000662:veterinary; D056831:Coordination Complexes; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D004285:Dogs; D019583:Dose Fractionation, Radiation; D064847:Multimodal Imaging / Q000379:methods / Q000662:veterinary; D009669:Nose Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000662:veterinary*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy / Q000662:veterinary; D010255:Paranasal Sinus Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy / Q000662:veterinary; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods / Q000662:veterinary*; D013882:Thiosemicarbazones / Q000493:pharmacokinetics*; D014057:Tomography, X-Ray Computed / Q000379:methods / Q000662:veterinary
chemical_list: D056831:Coordination Complexes; D015224:Dideoxynucleosides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C002854:alovudine