18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models

Anuradha Soundararajan, Jinu Abraham, Laura D. Nelon, Suresh I. Prajapati, Lee Ann Zarzabal, Joel E. Michalek, Stanton F. McHardy, Douglas S. Hawkins, Suman Malempati, Charles Keller

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9 Scopus citations

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 18F-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). Procedure: 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 200nM, respectively). Animals of each model were then treated with 80mg/kg/day PPP by intraperitoneal injection for 12 days and imaged by 18F-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: 18F-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.

Original languageEnglish (US)
Pages (from-to)485-492
Number of pages8
JournalPediatric Blood and Cancer
Volume59
Issue number3
DOIs
StatePublished - Sep 1 2012

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Keywords

  • Efficacy
  • FDG
  • Imaging
  • MicroPET
  • Picropodophyllin
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Soundararajan, A., Abraham, J., Nelon, L. D., Prajapati, S. I., Zarzabal, L. A., Michalek, J. E., McHardy, S. F., Hawkins, D. S., Malempati, S., & Keller, C. (2012). 18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models. Pediatric Blood and Cancer, 59(3), 485-492. https://doi.org/10.1002/pbc.24075