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Limitations of radioactive microspheres as tracers for bone blood flow and extraction ratio studies
Abstract:
Radioactive microspheres have been used for measuring bone blood flow and the extraction ratios of bone-seeking radionuclides, but we have shown that the technique is not completely valid. Bone uptake of 18F and 85Sr was compared with that of microspheres simultaneously injected into the heart or aorta of rats and rabbits under a variety of conditions. In single-passage experiments with quick killing to avoid recirculation, attention was focused on the tibiae and femora which could be dissected quickly to avoid post-mortem migration. For the rest of the skeleton, the effect of the latter was minimized by allowing recirculation for 5 min and comparing blood flow determinations in conjunction wit a cardiac output measurement. The apparent extraction ratio of 18F was variable and always exceeded unity in the single-passage experiments. With recirculation, there were significant differences between the extraction ratios for some bones, and the ratios sometimes exceeded unity. Extraction ratios for 85Sr were similarly variable, but lower. When 85Sr was compared directly with 18F, the relative extraction ratio was 0.8, with little variation between bones or animals. It is concluded that the flux of microspheres entering the vasculature of bone is not representative of blood flow, owing to the removal of some microspheres in pre-osseous capillary beds. Microspheres are therefore not a satisfactory standard for the determination of extraction ratios.
Insights
Radioactive microspheres are not ideal for measuring bone blood flow or radionuclide extraction ratios. Microsphere flux in bone vasculature doesn't accurately reflect blood flow due to pre-osseous capillary removal.
Area of Science:
- Nuclear Medicine
- Physiology
- Biomedical Engineering
Background:
- Radioactive microspheres are a common method for assessing bone blood flow and radionuclide extraction.
- Previous studies have indicated potential limitations in the accuracy of this technique.
Purpose of the Study:
- To evaluate the validity of using radioactive microspheres for measuring bone blood flow and extraction ratios.
- To compare the uptake of bone-seeking radionuclides (18F and 85Sr) with microsphere distribution in bone.
Main Methods:
- Simultaneous injection of radioactive microspheres and bone-seeking radionuclides (18F, 85Sr) into the heart or aorta of rats and rabbits.
- Single-passage experiments with rapid tissue dissection and experiments with recirculation.
- Comparison of radionuclide uptake with microsphere distribution in tibiae, femora, and the rest of the skeleton.
Main Results:
- Apparent extraction ratios for 18F were variable and often exceeded unity in single-passage experiments.
- Significant differences in extraction ratios were observed with recirculation, sometimes exceeding unity.
- Extraction ratios for 85Sr were variable and lower than 18F, with a relative extraction ratio of 0.8 when directly compared.
Conclusions:
- Microsphere flux in bone vasculature does not accurately represent blood flow due to removal in pre-osseous capillary beds.
- Radioactive microspheres are not a suitable standard for determining extraction ratios in bone.
- The technique's limitations necessitate alternative methods for accurate bone blood flow and extraction ratio measurements.

