18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models.
18F-FDG microPET imaging detects early transient response to an IGF1R inhibitor in genetically engineered rhabdomyosarcoma models.
复制标题
18F-FDG microPET 成像可检测基因工程横纹肌肉瘤模型中对 IGF1R 抑制剂的早期瞬时反应。
DOI：
10.1002/pbc.24075
复制
发表时间：
2012
影响因子：
3.2
通讯作者：
Keller,Charles
中科院分区：
文献类型：
--
作者：
Soundararajan,Anuradha;Abraham,Jinu;Nelon,LauraD;Prajapati,SureshI;Zarzabal,LeeAnn;Michalek,JoelE;McHardy,StantonF;Hawkins,DouglasS;Malempati,Suman;Keller,Charles
BackgroundAlveolar 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 of18F‐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).ProcedurePrimary tumor cell cultures fromMyf6Cre,Pax3:Fkhr,p53andPax7CreER,Ptch1,p53conditional models of ARMS and ERMS/UPS were found to be highly sensitive to PPP (IC50values 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 by18F‐FDG microPET.ResultsTumor 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.Conclusions18F‐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. Pediatr Blood Cancer 2012;59:485–492. © 2012 Wiley Periodicals, Inc.
