Simultaneous PET/SPECT imaging to compare tumor uptake level of 18F-FMISO with 64Cu-ATSM on the basis of the genetic activation level responding to tumor hypoxia

Objectives Previous reports suggested that the tumor uptake levels of hypoxia PET tracers 18F-FMISO and 64Cu-ATSM were both related to prognosis, but also that their intratumoral distributions were different. The purpose of this study was to compare tumor uptake level of 18F-FMISO with 64Cu-ATSM on the basis of the 99mTcO4- uptake level genetically responding to tumor hypoxia in simultaneous PET/SPECT imaging.

Methods Human colon carcinoma HCT116 cells were stably transfected with a sodium/iodide (NIS) reporter gene controlled under 12 hypoxia responsive elements (HRE), and were injected subcutaneously into the mice. Three weeks later, simultaneous PET/SPECT imaging was performed using U-SPECT-II/CT with clustered-multipinhole collimator that enabled simultaneous acquisition of single-photon and positron emitting radiolabeled molecules. We injected intravenously with a mixture of 18F-FMISO and 99mTcO4− or a mixture of 64Cu-ATSM and 99mTcO4− after housing under hypoxia (10% O2), normoxia or hyperoxia (80% O2). The uptake levels were estimated as standardized uptake value (SUV).

Results The tumor SUVmax was significantly increased with decreasing oxygen concentration. The positive correlations were significantly found between tumor SUVmax of PET tracers and that of 99mTcO4- (18F-FMISO and 99mTcO4-: r = 0.91, p < 0.0001, 64Cu-ATSM and 99mTcO4-: r = 0.74, p = 0.0005).

Conclusions The correlation between tumor SUVmax of both PET tracers and genetic activation level by HIF-1 supported the previous reports that the uptake levels of 18F-FMISO and 64Cu-ATSM were both related to prognosis. The tumor uptake levels of both PET tracers indirectly reflected the HIF-1 induced resistance to therapy, and were reliable diagnostic factors for the outcome prediction and treatment planning.