In this study, we showed that quantification in bone scintigraphy could help in distinguishing prostate cancer bone metastases from spinal and pelvic osteoarthritic changes, and therefore increase bone scan specificity. Using an optimum SUVmax cutoff of 19.5 g/mL for defining lumbar and pelvic bone metastases on SPECT/CT, bone scan yielded a sensitivity, specificity, positive and negative predictive values of 87%, 92%, 99% and 49%, respectively.
To the best of our knowledge, only few studies previously reported on the quantification of 99mTc-DPD uptake in bone metastases of prostate cancer patients. Beck et al. showed that the mean SUVpeak of metastatic lesions in breast and prostate cancer patients was 20.4 ± 20.8 g/mL . This difference is at least partly due to the fact that SUVpeak is usually lower than SUVmax. Moreover, patients included in their study were both prostate and breast cancer patients combined, with a majority of the latter. Since breast cancer metastases are both osteoblastic and osteolytic, their uptake is probably lower than that of prostate cancer metastases, which are mostly osteoblastic as in our patient population. SUVs were further higher in our study than those reported by Umeda et al., who found a lower threshold of 7 g/mL of SUVmax, above which the tumor burden of metastatic prostate cancer patients was determined . Kuji et al. reported a high accuracy of quantitative SPECT/CT for the diagnosis of bone metastases in 170 prostate cancer patients . They used a different reconstruction algorithm based on CT zonal mapping and included only the three hottest lesions explaining a slightly higher SUVmax and SUVmean (SUVmax of 35 ± 25 g/mL in our study versus 41 ± 34 g/mL in the study by Kuji et al., and a mean SUVmean of 21 ± 15 g/mL versus 24.6 ± 21.2 g/mL, respectively). We had similar quantitative results compared to Kuji et al. regarding radiotracer uptake by spinal osteoarthritic changes with a mean SUVmax of 14.2 ± 3.8 g/mL compared to 16.7 ± 6.7 g/mL, and a mean SUVmean of 8.9 ± 2.2 g/mL compared to 9.5 ± 3.9 g/mL, respectively. Interestingly, SUVs were comparable although the radiotracers used for the bone scan were slightly different: 99mTc-DPD versus 99mTc-methylene diphosphonate (99mTc-MDP) in the Kuji et al. study. Thus, SUVs seem not only comparable from one center to another but also comparable regardless of which type of diphosphonate is used. This is further reinforced by comparable lumbar vertebrae SUVmean in our study compared to the vertebral SUVmean in the study by Cachovan et al. (SUVmean 6.9 ± 1.9 in our study versus 5.91 ± 1.54 in the Cachovan et al. study) .
In our study, SUVmax and SUVmean of metastatic lesions varied depending on the lesion location, with lowest values in the ribs and scapular girdle, which is similar to the observations from Beck and al. . This is probably at least partly due to the size of the lesions, which tend to be smaller in the ribs and scapular girdle with partial volume effect, as described for PET . Different vascularization and osteoblastic reaction in these different anatomical regions may also play a role. There was no significant difference in SUVmax and SUVmean between metastatic lesions in the ribs, scapular girdle and extremities, and osteoarthritic lesions; hence, no cutoff value could be obtained to distinguish between them. For lesions in the spine and pelvis, we found an optimum SUVmax cutoff of 19.5 g/mL with a very high sensitivity and positive predictive value. We believe this cutoff could be of added diagnostic value enabling physicians to decide with a high accuracy that a focal 99mTc-DPD uptake in the spine or pelvis above 19.5 g/mL is most likely to be metastatic in a patient with known prostate cancer.
In this study, SUVmax was significantly lower in lumbar and pelvic bone metastases of patients relapsing after prior systemic therapy compared to patients with no previous systemic treatment. This is not surprising as previous treatment may induce sclerosis, reduced vascularization, or other tumor environment changes, which can all influence 99mTc-DPD uptake. Understanding the mechanism of reduced uptake in these lesions may help better understand the bone tumor microenvironment of prostate metastases . Interestingly, the SUVmax cutoff of 19.5 g/mL still had a high positive predictive value for spinal and pelvic bone metastases in patients having received prior treatment for bone metastases.
There are of course other nuclear medicine modalities available for the detection and characterization of bone metastases in prostate cancer patients. 68Ga-prostate specific membrane antigen (PSMA), 18F-choline and 18F-sodium fluoride (NaF) PET/CT all have very good accuracies for the diagnosis of prostate cancer bone metastases [14-17]. The most promising modality seems to be 68Ga-PSMA PET/CT [18, 19]. Nonetheless, in many countries, 68Ga-PSMA, 18F-Choline and 18F-NaF PET are not widely available for primary staging due to cost and reimbursement issues, as impact on patient management and cost-effective studies are not yet available . A study comparing PSA cutoff value for ordering 18F-NaF PET or bone scintigraphy in patients with newly diagnosed prostate cancer showed no major difference between both modalities . Furthermore, a recent study by Arvola et al. showed a strong correlation between SUVs from 99mTc-HDP SPECT/CT and 18F-NaF PET/CT . The authors concluded that SPECT is an applicable tool for clinical quantification of bone metabolism in osseous metastases in breast and prostate cancer patients.
Therefore, quantitative bone scintigraphy seems to increase bone SPECT/CT accuracy, allowing bone scintigraphy to remain competitive in the era of new multimodality imaging of bone metastases in prostate cancer patients. We believe that the SUVmax cutoff of 19.5 mg/L for spinal and pelvic lesions could further increase bone scan specificity.
The main limitations of our study are the small subject population and the lack of histological confirmation for all prostate cancer bone metastases. However, as authors reported that histological confirmation may be avoided in the case of typical morphological imaging findings and patterns of radiotracer uptake , lesions were thus diagnosed as metastatic on conventional SPECT/CT and were subsequently analyzed for tracer uptake quantification. In addition, since we proceeded with a lesion-based analysis, the relatively small number of patients did not allow correlating further the level of uptake with the different histological grades of prostate cancer.