In this study, we assessed the SUV of 99mTc-MDP in normal vertebrae, benign bone lesion and malignant bone metastasis foci using quantitative SPECT/CT in 221 patients. For normal vertebrae, we evaluated the SUVmax, SUVmean and CT value (HU) of all the 24 vertebral segments in male and female patients. It showed that SUVmax in male patients were markedly higher than those in females. In addition, we found that SUVmax of three vertebral regions in male patients also showed statistically differences. When comparing SUVmax in different vertebral regions between male and female patients, SUVmax were proved to be significantly different between male and female patients in cervical, thoracic and lumber vertebrae. This reminds us that to establish a quantitative diagnostic reference for differentiating vertebral lesions, lesions should be categorized based on gender and vertebral regions to compare the SUVmax.
Cachovan et al.  used SPECT/CT bone quantification to obtain the mean SUVmax of Tc-99m diphosphono-sponge propanedi-carboxylic acid (99mTc-DPD) of L3-5 vertebral trabecular bone in 50 females (mean ± SD = 5.91 ± 1.54). In our study, the mean SUVmax of lumbar in female participants was 7.04 ± 1.47, which was slightly higher than the value obtained by Cachovan et al. The small different results may due to the different tracer kinetics. Furthermore, in our study, the VOI contained the cortical bone with high bone salt metabolism which could lead to the increased SUVmax. The SUVmax of normal vertebra in our study was similar to the previously reported studies which also included bone cortex in their VOIs [11, 13,14,15,16,17,18]. It is well known that bone lesions including tumors, inflammation and other diseases often ended up with cortical hyperplasia [18, 19]. Therefore, we suggest the inclusion of cortical bone within the VOI for quantitative analysis.
Besides, we analyzed the correlation between SUVmax of normal vertebrae and CT values (HU), age, height, weight, BMI in male and female patients. It comes out that SUVmax of normal vertebrae showed a strong negative correlation with CT values in both men and women. The SUVmax of normal vertebrae also showed significant correlation with weight, height and BMI in male patients, and significant correlation with weight and BMI in female patients.
Hounsfield Unit (HU) is a commonly used measurement index in CT images that indicates the X-ray attenuation degree in tissue (also known as bone density). Bone mineral density (BMD) obtained through dual energy X-ray absorptiometry (DEXA) is the gold standard for the measurement of BMD in clinic . There is still controversy about the relationship between HU and SUV. Previous studies demonstrated a significant positive correlation between HU and BMD [10, 11] [21,22,23,24], which was opposite to our findings. To figure out the reason leading to this controversial result, we found that previous studies only analyzed relationship in the lumbar vertebral region. As shown in Fig. 3, HU showed a decreasing trend from cervical to lumbar vertebra. In the meanwhile, SUVmax didn’t show clear changing trend. SUVmax of 99mTc-MDP in bone is often associated with blood supply and osteoblastic activity . The blood supply of the lumbar artery from the abdominal aorta is richer than that from the vertebral artery . Subjected by gravity and effected by weight, pressure increased from cervical to lumbar leading to more osteoblastic activity in lumber vertebra . And due to the anatomical structure, pressure load of lumbar is predominantly static, while cervical is mainly dynamic. In addition, the cervical spine also needs to move in all three planes. The distribution of tension lines in different directions leads to a denser trabecular structure in the cervical . Hence BMD of lumbar vertebra was lower than the cervical vertebra resulting in a lower CT HU value, while richer blood supply in lumbar enhanced the tracer uptake. Besides, the age of the subjects, imaging parameters and reconstruction algorithm in different experiments may also lead to different results. Our results were consistent with some other studies [23, 24]. Israel et al.  found that the 99mTc-MDP uptake in bone cortex of osteoporotic women was higher than that of non-osteoporotic women, suggesting that the bone loss in osteoporosis patients may increase bone conversion, leading to the increase of the bone cortex uptake of 99mTc-MDP. Fogelman et al.  performed SPECT on young women after ovariectomy and found a negative correlation between MDP distribution and BMD. As Table 1 showed, the mean age in our study was 66.3 of male and 62.8 of female. With an increasing possibility of calcium loss, the negative correlation between SUVmax and CT value was observed. It suggests, using hybrid imaging of SPECT/CT, combining SUVmax and CT value (HU) could be used as a potential biological indicator for the evaluation of osteoporosis, and establishing the SUVmax and HU of normal vertebral bodies should be taken into consideration. But the mechanism underlying this correlation still need further investigation.
The relationship of SUV and height and weight also showed opposite results with previous studies [7, 9, 11]. It has been reported that SUVmax of vertebra was independent with height. Maybe the limited sample size in previous studies lead to the controversial results. With a large sample size, our results showed that SUVmax was positively correlated with the height, weight in men and positively correlated with the weight in women which further validated the hypothesis proposed by Kaneta et al.  that the increased pressure leads to more blood supply, thus resulting in the increasing of SUVmax. We also found that SUVmax was positively correlated with BMI. To our knowledge, few studies have reported such a relationship. A PET/CT study using 18F-NaF assessed the effects of BMI on knee joint inflammation and found a positive correlation between 18F-NaF uptake in knee joint and BMI, which was similar with our findings . It is also potentially caused by the increased mechanical loading which increased the blood supply and bone turnover, and as a result an increasing tracer uptake. But further research is required to clarify these findings. In our study, the SUVmax and SUVmean were significantly higher in men than those in women. This might also due to the height of women in our study was generally lower than men. Since the number of patients in each age group was not evenly distributed by height, we did not find a correlation between SUVmax and age.
With the established reference of SUVmax in normal vertebrae (Table 2), SUVmax of bone lesions were compared with normal reference to verify the differentiating diagnostic value of quantitative SPECT/CT in bone scanning. Our results demonstrated that SUVmax of normal vertebrae, benign bone lesion and malignant bone metastasis foci were significantly different from each other in thoracic and lumbar regions of male and female patients. The results were consistent with previous studies [16, 17], which verified the differentiating diagnostic value of SUVmax in bone lesions using SPECT/CT. Different from previous studies, based on our findings in normal vertebrae, data comparison was performed on lesions in different gender and vertebral region groups. Hence, we suggest quantitative diagnose of bone lesions using SPECT/CT should take gender and vertebral regions into consideration. These results also remind us that quantitative SPECT/CT may be of great value in therapy monitoring.
Our study has some limitations. Firstly, although age distribution was wide, the uneven distribution of research object number of each age group could make it hard to reflect the SUVmax of all ages. Secondly, the SUVmax acquired in our study was based on body weight. Since the 99mTc-MDP uptake mainly exists in bone, the standardization of bone volume can improve the accuracy of quantification . This indicated that bone volume should be included in future studies. In addition, the quantitative accuracy of bone imaging is also affected by the reconstruction parameters. Previous studies have shown that quantitative values increase with higher number of iterations . Therefore, in future studies, we will further expand the sample size and stratify experimental subjects according to age, height and BMI. We will further optimize reconstruction parameters such as increasing the number of iterations to obtain more accurate bone quantitative standard values. Although CT value (HU) was evaluated in normal vertebrae, we didn’t investigate the diagnostic value of combination of SUVmax and HU in differentiating bone lesions. This is a promising topic in quantitative SPECT/CT, we will explore its potential diagnostic value in the future.