The purpose of this study was to develop a longitudinal non-invasive functional imaging method using a dual-radioisotope hybrid micro-positron emission tomography/computed tomography (PET/CT) scanner in order to assess both the skeletal metabolic heterogeneity and the effect of localized radiation that models therapeutic cancer treatment on marrow and bone metabolism. Skeletally mature BALB/c female mice were given clinically relevant local radiation (16 Gy) to the hind limbs on day 0. Micro-PET/CT acquisition was performed serially for the same mice on days -5 and +2 with FDG and days -4 and +3 with NaF. Serum levels of pro-inflammatory cytokines were measured. Significant differences (p < 0.0001) in marrow metabolism (measured by FDG) and bone metabolism (measured by NaF) were observed among bones before radiation, which demonstrates functional heterogeneity in the marrow and mineralized bone throughout the skeleton. Radiation significantly (p < 0.0001) decreased FDG uptake but increased NaF uptake (p = 0.0314) in both irradiated and non-irradiated bones at early time points. An increase in IL-6 was observed with a significant abscopal (distant) effect on marrow and bone metabolic function. Radiation significantly decreased circulating IGF-1 (p < 0.01). Non-invasive longitudinal imaging with dual-radioisotope micro-PET/CT is feasible to investigate simultaneous changes in marrow and bone metabolic function at local and distant skeletal sites in response to focused radiation injury. Distinct local and remote changes may be affected by several cytokines activated early after local radiation exposure. This approach has the potential for longer-term studies to clarify the effects of radiation on marrow and bone.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (1R01CA154491-01, 1R03AR055333-01A1, and 1K12-HD055887-01) and the Japan Society for the Promotion of Science Core to Core Program (23003). This work was also supported by PHS Cancer Center Support Grant P30 CA77398 and the Joseph E. Wargo Cancer Research Fund from the University of Minnesota. C. J. R. received funding support from the National Institutes of Health (R24DK092759). The authors acknowledge and thank Dr. Kihak Lee (Siemens Medical Solutions, Knoxville, TN) for advice and fruitful discussion pertaining to this experiment and report, Dr. Bruce E. Hammer (Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN) for help with the Siemens micro-PET/CT scanner, and Phuong T. Le (Maine Medical Center Research Institute, Scarborough, ME) for the measurement of pro-inflammatory markers.
- Translational research