Correlation between intracellular hypoxia and ineffective neovascularization with increase of concentration of hemoglobin in breast cancer measured by ¹⁸F-fluoroimizadole PET/CT and diffusion optical spectroscopy

Objectives The concentrations of oxygenated hemoglobin (HbO₂) and deoxygenated hemoglobin (Hb) have been measurable by infrared and near-infrared diffusion optical spectroscopy (DOS). The intracellular hypoxic status is also evaluable by ¹⁸F-fluoroimizadole (FMISO) PET. The aim of this study was to evaluate the relationship between the concentration of total hemoglobin and oxygen saturation measured by DOS and intracellular hypoxia measured by FMISO PET.

Methods The subjects were twenty-seven patients with breast cancer who underwent both DOS and FMISO PET/CT before therapy. The concentrations of HbO₂ and Hb in the tumor and normal breast tissue were obtained by DOS measurement, and then the concentrations of total hemoglobin (tHb) and oxygen saturation (stO₂) were derived the concentrations of HbO₂ and Hb. The uptake of FMISO was evaluated as SUVmax. The each relative value (Δ) was obtained as difference value between tumor and normal breast tissue.

Results The measured values were shown in Table. There were correlations between the relative concentration (ΔHbO₂, ΔHb, ΔtHb) of each Hb and ΔFMISO SUVmax (r=0.44, p=0.018; r=0.46, p=0.013; r=0.45, p=0.014). On the other hand, there was no correlation between ΔstO₂ and ΔFMISO SUVmax (r=0.13, p=0.5).

Conclusions There was no relationship between extracellular hypoxia demonstrated by DOS and intracellular hypoxia demonstrated by FMISO PET. On the other hand, the relative concentrations of each Hb in tumor to those in normal tissue had positive correlations to FMISO uptake. It is suggested that intracellular hypoxia in the tumor would induce hyperemia due to ineffective neovascularization resulting the maintenance of oxygen saturation around the tumor cells, but the tumor cells might still be intracellularly hypoxic.