title: Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study.
abstract: BACKGROUND
  Glycolytic activity and hypoxia are associated with poor prognosis and radiation resistance. Including both the tumor uptake of 2-deoxy-2-[18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer copper(II)diacetyl-bis(N4)-methylsemithio-carbazone (Cu-ATSM) in targeted therapy planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of 64Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV).
  
  
  METHODS
  Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUVmax. The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy, the possible dose boost (DB) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and 64Cu-ATSM sub-volumes.
  
  
  RESULTS
  The potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2.4-54.3%), FDG40 45.2% (10.1-75.2%), and FDG50 32.5% (2.6-68.1%). A BTV including the union (∪) of Cu3 and FDG would involve boosting to a larger fraction of the GTV, in the case of Cu3∪FDG40 63.5% (51.8-83.8) and Cu3∪FDG50 48.1% (43.7-80.8). The union allowed only a very limited DB whereas the intersection allowed a substantial dose escalation.
  
  
  CONCLUSIONS
  FDG and 64Cu-ATSM sub-volumes were only partly overlapping, suggesting that the tracers offer complementing information on tumor physiology. Targeting the combined PET positive volume (BTV) for dose escalation within the GTV results in a limited DB. This suggests a more refined dose redistribution based on a weighted combination of the PET tracers in order to obtain an improved tumor control.
authors.affiliation: Department of Radiation Oncology, Rigshospitalet, Section 3994, Blegdamsvej 9, 2100 Copenhagen, Denmark. mmc@sund.ku.dk.
authors.forename: Malene M
authors.initials: MM
authors.lastname: Clausen
authors.forename: Anders E
authors.initials: AE
authors.lastname: Hansen
authors.forename: Per Munck
authors.initials: PM
authors.lastname: Af Rosenschold
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
authors.forename: Annemarie T
authors.initials: AT
authors.lastname: Kristensen
authors.forename: Fintan J
authors.initials: FJ
authors.lastname: McEvoy
authors.forename: Svend A
authors.initials: SA
authors.lastname: Engelholm
mesh_terms: D000465:Algorithms; D000818:Animals; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D006019:Glycolysis; D000860:Hypoxia; D064847:Multimodal Imaging; D009369:Neoplasms / Q000378:metabolism*; D016011:Normal Distribution; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011880:Radiotherapy Planning, Computer-Assisted; D013882:Thiosemicarbazones / Q000737:chemistry / Q000493:pharmacokinetics*; D014057:Tomography, X-Ray Computed
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18