PET/MR imaging and optical imaging of metastatic rhabdomyosarcoma in mice

The combination of PET and MR imaging synergizes molecular and morphologic information, allowing better diagnosis in cancer patients. The diagnosis of tumor recurrence in rhabdomyosarcoma is extremely challenging and could be improved with PET/MR imaging. The aim of this study was to validate PET/MR imaging in a disseminated rhabdomyosarcoma mouse model.

One million alveolar (Rh30) and embryonal (RD) rhabdomyosarcoma cells with stably transfected mCherry and Gaussia luciferase were injected intraperitoneally into NOD/LtSz-scid-IL2Rγnull mice. Nine animals were treated with vincristine (0.75 μg/g/d). Tumor growth was monitored on the basis of serum luciferase activity, optical imaging (OI) of the fluorescent protein mCherry, and sequential PET/MR imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and (18)F-FDG. Immunohistochemical Ki-67 and glucose transporter 1 analysis was used to evaluate tumor cell density and proliferative and metabolic activity.

The injection of rhabdomyosarcoma cells led to intraperitoneal tumor growth in 34 of 37 mice (Rh30) and 4 of 9 animals (RD). OI revealed inconsistent results for tumors located near the liver. The detection of tumors in the peritoneal cavity was exclusively possible with sequential PET/MR imaging. PET studies with (18)F-FLT MR imaging were more reliable than (18)F-FDG comparing the tracer uptake and correlation with tumor weight. Treatment with vincristine led to reduced tumor growth, which was efficiently detected with (18)F-FDG PET and MR imaging. Total tumor burden as estimated by PET/MR imaging correlated with the serum luciferase activity.

We established a unique model of metastatic rhabdomyosarcoma with a high frequency of tumor occurrence and easy monitoring of the tumor growth based on reporter gene expression. The accurate detection of rhabdomyosarcoma requires high soft-tissue contrast provided by the MR imaging and high tracer uptake for PET, which was achieved with (18)F-FLT as the tracer before and (18)F-FDG after treatment with vincristine. PET/MR imaging allows improved diagnosis of experimental rhabdomyosarcoma and therefore might influence clinical therapeutic decisions in the future.