title: 18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models.
abstract: BACKGROUND
  Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) are among the most common and most treatment resistant soft tissue sarcomas of childhood. Here, we evaluated the potential of (18)F-Fluorodeoxyglucose (FDG) as a marker of therapeutic response to picropodophyllin (PPP), an IGF1R inhibitor, in a conditional mouse model of ARMS and a conditional model of ERMS/undifferentiated pleomorphic sarcoma (UPS).
  
  
  METHODS
  Primary tumor cell cultures from Myf6Cre,Pax3:Fkhr,p53 and Pax7CreER,Ptch1,p53 conditional models of ARMS and ERMS/UPS were found to be highly sensitive to PPP (IC(50) values 150 and 200 nM, respectively). Animals of each model were then treated with 80 mg/kg/day PPP by intraperitoneal injection for 12 days and imaged by (18)F-FDG microPET.
  
  
  RESULTS
  Tumor volumes on day 4 for PPP-treated ARMS and ERMS mice were lower than untreated control mouse tumor volumes, although treated tumors were larger than day 0. However, tumor FDG uptake was significantly reduced on day 4 for PPP-treated mice compared to pretreatment baseline or untreated control mice on day 4 (P < 0.05). Nevertheless, by day 12 tumor volumes and FDG uptake for treated mice had increased significantly, indicating rapidly evolving resistance to therapy.
  
  
  CONCLUSIONS
  (18)F-FDG PET imaging is a potential imaging biomarker of molecular susceptibility to targeted agents early in treatment for this aggressive form of sarcoma, but may find best use serially for Phase I/II studies where chemotherapy and targeted agents are combined to cytoreduce tumors and abrogate Igf1r inhibitor resistance.
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Soundararajan
authors.forename: Jinu
authors.initials: J
authors.lastname: Abraham
authors.forename: Laura D
authors.initials: LD
authors.lastname: Nelon
authors.forename: Suresh I
authors.initials: SI
authors.lastname: Prajapati
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Zarzabal
authors.forename: Joel E
authors.initials: JE
authors.lastname: Michalek
authors.forename: Stanton F
authors.initials: SF
authors.lastname: McHardy
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Hawkins
authors.forename: Suman
authors.initials: S
authors.lastname: Malempati
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D051379:Mice; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000188:drug therapy*
chemical_list: C415032:picropodophyllin; D019788:Fluorodeoxyglucose F18; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin