Comparison of FDG PET and SPECT for Detection of Bone Metastases in Breast Cancer
Abstract
OBJECTIVE. The purpose of our study was to evaluate the efficacy of FDG PET and bone SPECT for diagnosing bone metastases in breast cancer.
SUBJECTS AND METHODS. The study was a prospective series of 15 patients with breast cancer who underwent both PET and bone scanning with SPECT. Comparison was performed on a lesion-by-lesion analysis. MDCT, MRI, and the patient's clinical course were used as references.
RESULTS. In the lesion-by-lesion analysis (n = 900), the sensitivity for diagnosing bone metastases was 85% for SPECT and 17% for PET, specificity was 99% for SPECT and 100% for PET, and accuracy was 96% for SPECT and 85% for PET. In the statistical analysis, bone SPECT was significantly superior to FDG PET for its sensitivity (p < 0.0001) and accuracy (p < 0.0001). No statistically significant difference was seen with regard to specificity. When classifying the bone metastases as osteoblastic or osteolytic, bone scanning classified 92% of metastases as osteoblastic and 35% of metastases as osteolytic, whereas PET classified 6% of metastases as osteoblastic and 90% of metastases as osteolytic.
CONCLUSION. Bone SPECT is superior to FDG PET in detecting bone metastases in breast cancer. The sensitivity of osteoblastic lesions is limited with FDG PET. Surveillance of metastatic spread to the skeleton in breast cancer patients based on FDG PET alone is not possible.
Introduction
Bone is the most common site of breast cancer metastasis. Up to 90% of patients who have terminal distant breast cancer have bone metastasis. Bone is also the most frequent site of recurrence after treatment for primary breast cancer [1-3]. In patients with breast cancer, bone metastases do not necessarily mean a poor short-term prognosis. The duration of survival of patients with visceral involvement is much shorter, usually a matter of a few months [4]. Therefore, diagnosis and treatment of bone metastases before the development of significant neurologic and functional deficits might improve the outcome in breast cancer patients. Appropriate imaging can assist in the early detection of bone metastases.
Radionuclide bone scanning has been the standard initial imaging method for detection of skeletal metastases because of its great sensitivity and its ability to examine the whole skeleton in a single examination [5]. However, some reports indicate that bone scanning is less effective than FDG PET for detecting bone metastases in breast cancer [6-9], whereas other reports indicate that FDG PET has a lower sensitivity for detecting breast cancer bone metastases than bone scanning [10-11]. Therefore, FDG PET has not yet found a role in the clinical evaluation of bone metastases in breast cancer. Moreover, in these studies, bone planar imaging, not bone SPECT, was compared with FDG PET. Bone SPECT has proven to be superior to planar imaging in detecting various bone diseases [12-16]. Because no studies comparing bone SPECT and FDG PET have been reported, it is not clear whether FDG PET is a more powerful tool than bone SPECT in the clinical evaluation of breast bone metastases. The purpose of this study was to show similarities and discrepancies between FDG PET and bone SPECT for detecting bone metastases in breast cancer and to evaluate the efficacy of FDG PET and bone SPECT in diagnosing bone metastases in breast cancer.
Subjects and Methods
Our study was a prospective series of 15 patients with breast cancer who underwent both FDG PET and bone scanning within 49 days (mean, 20 days). Eight patients were evaluated for restaging and seven for initial staging. Metastatic bone disease was previously known to be present in three patients (Table 1). Our institutional review board approved the protocol, and written informed consent was obtained from all patients.
| Patient No. | Age | UICC Stage | Indication for Skeletal Survey | Metastases | |
|---|---|---|---|---|---|
| Osteoblastic | Osteolytic | ||||
| 1 | 56 | 2B | Staging | 0 | 0 |
| 2 | 53 | 2B | Staging | 0 | 0 |
| 3 | 63 | 4 | Staging, lung metastases | 41 | 0 |
| 4 | 50 | 2B | Staging | 0 | 0 |
| 5 | 53 | 1 | Restaging | 0 | 0 |
| 6 | 39 | 2A | Staging | 0 | 1 |
| 7 | 62 | 4 | Restaging, skin metastases | 28 | 3 |
| 8 | 52 | 1 | Restaging, bone and liver metastases | 2 | 4 |
| 9 | 50 | 4 | Restaging, bone pain | 0 | 0 |
| 10 | 59 | 1 | Staging | 0 | 0 |
| 11 | 43 | 0 | Staging | 0 | 0 |
| 12 | 44 | 2B | Staging | 0 | 0 |
| 13 | 68 | 2B | Restaging, bone metastases | 5 | 2 |
| 14 | 46 | 1 | Restaging, bone and liver metastases | 35 | 0 |
| 15 | 62 | 2A | Restaging, liver metastases | 32 | 10 |
Note. —UICC = International Union Against Cancer.
Bone Scanning
Two modern double-head gamma cameras (ECAM, Siemens Medical Solutions) were used. The axial field of view was 40 cm for both cameras. Low-energy, high-resolution collimators were used for planar images and for SPECT. Data acquisition was 2-5 hr after the IV injection of 740 MBq of 99mTc hydroxymethylenediphosphonate (HMDP). Two additional SPECT acquisitions of the cervicothorachic and thoracolumbar spine were performed for all patients. For SPECT, a double-head gamma camera (128 × 128 matrix; 68 steps; 15 sec or 18 sec per step; Butterworth filter) was used. The total acquisition time was 13-15 min for planar imaging and approximately 20 min for SPECT. Reconstruction was performed with the ordered subset expectation maximization.
FDG PET
FDG PET was performed using a modern PET camera (Advance NXi; GE Healthcare). Patients fasted for 4 hr before scanning. Emission scanning was started 60 min after the injection of 220-240 MBq of FDG. The FDG PET scans included six or seven bed positions (5-min acquisition time per position; total acquisition time, 30-35 min) covering from the skull to the proximal femur. The results of postemission transmission scans were used to correct for attenuation. Standardized uptake values were not calculated in this study.
Classification of Bone Metastases
Breast cancer metastases to bone may manifest radiographically as osteolytic, osteoblastic, and mixed lesions. However, it is difficult to objectively classify bone metastases as mixed types. In this study, bone metastases were categorized as osteolytic or osteoblastic from CT images. So-called mixed bone metastases were classified as osteoblastic in this study.
Sites of Bone Metastases
Tumor cells most frequently affect the heavily vascularized areas of the skeleton, particularly the red bone marrow of the axial skeleton and the proximal ends of the long bones, the ribs, and the vertebral column [17]. The spine is the most frequent site of cancer metastases; the posterior elements, including the pedicle, are the area of the vertebral body most frequently involved [18]. Moreover, breast cancer has a special predilection for the sternum that probably results from local spread from metastatic internal mammary nodes [5]. Therefore, we limited out evaluation to the axial skeleton: that is, the vertebral column (24 vertebrae of C1-L5, one sacrum including coccyx), the pelvis (two each ilia, ischia, and pubes), the sternum, and the proximal ends of the long bones (two each humeri and femora), and the ribs (n =24). We evaluated a total of 60 bones per patient.
Definition of Bone Metastases
Commercially available MDCT (Aquilion, Toshiba), MRI (Signa Twin Speed, GE Yokogawa Medical Systems), and clinical course were used as references. MRI sequences used to evaluate bone metastases typically are T1-weighted and STIR techniques, if neccessary, using gadolinium-enhanced T1-weighted images. Patients were defined as having no bone metastases when FDG PET, bone scanning, MRI, or MDCT did not show bone metastases. In all cases, at least one other method, which included MDCT or MRI, confirmed that bone scanning and FDG PET findings were caused by metastatic disease. A clinical follow-up of more than 12 months was used to confirm the final results of analysis of the bone metastases.
Data Analysis
Two experienced radiologists interpreted whole-body FDG PET images and another two experienced radiologists interpreted 99mTc HMDP whole-body bone scans with SPECT. The experienced radiologists were unaware of each other's findings. If two reviewers did not agree on the results, they discussed their differences and reached a consensus. PET images and bone scans were compared using a lesion-by-lesion analysis.
Statistical Analysis
The results of FDG PET and bone SPECT were analyzed statistically using the McNemar test.
Results
There were no findings on only bone SPECT or FDG PET but not confirmed by another technique. In the lesion-by-lesion analysis (n = 900), the results of the detection of bone metastases with the two techniques are shown in Table 2. The sensitivity for diagnosing bone metastases was 85% for SPECT and 17% for FDG PET, and specificity was 99% for SPECT and 100% for FDG PET. In the statistical analysis, bone SPECT was significantly superior to FDG PET in its sensitivity (p < 0.0001) and accuracy (p < 0.0001). No statistically significant difference was seen with regard to specificity.
| Bone SPECT | FDG PET | p | |
|---|---|---|---|
| Sensitivity (%) | 85 (139/163) | 17 (27/163) | <0.0001 |
| Specificity (%) | 99 (729/737) | 100 (737/737) | NS |
| Accuracy (%) | 96 (868/900) | 85 (764/900) | <0.0001 |
Note. —NS = not significant.
In the classification of the bone metastases as osteoblastic or osteolytic, bone scanning detected 132 (92%) of 143 osteoblastic metastases and seven (35%) of 20 osteolytic metastases, whereas FDG PET detected nine (6%) of 143 osteoblastic metastases and 18 (90%) of 20 osteolytic metastases.
Bone SPECT altered patient treatment in one of the 15 patients and radiation therapy was indicated. Using FDG PET, the bone metastasis was missed (Figs. 1A, 1B, 1C, 1D, 1E, and 1F).
When interpreted without bone SPECT, bone planar imaging correctly detected 116 (71%) of 163 lesions. Metastases outside the vertebral body (e.g., in the pedicle, lamina, and process) were more often detected on SPECT than on planar imaging.
Discussion
Bone scanning has great sensitivity for detecting bone metastases, but its specificity is relatively poor [5]. Fractures, degenerative disease, and benign disorders of the spine (Schmorl's nodes, hemangioma) all may be positive, because bone scanning relies on an osteoblastic reaction and blood flow [5]. SPECT is more accurate than planar imaging in the detection of bone abnormalities because SPECT reveals useful information that is helpful in differentiating benign from malignant lesions in the vertebrae because of the precise location of lesions on tomographic images [12-16]. Moreover, our data suggest that bone SPECT is superior to planar imaging in detecting metastases outside the vertebral body. In our study, bone SPECT had as good specificity as FDG PET and better sensitivity than FDG PET. The findings on bone SPECT altered treatment in one patient. The patient had a bone metastasis in the sternum that was missed on FDG PET but was seen on SPECT, MRI with contrast enhancement, and MDCT (Figs. 1A, 1B, 1C, 1D, 1E, and 1F). The result also might suggest that detection of small bone metastases was limited by the currently achievable spatial resolution of PET or because the bone metastasis had low metabolic activity. On the other hand, one patient had diffuse uptake in the cervical vertebral body on SPECT: we classified this vertebral lesion as malignant but MDCT revealed osteophytes of the vertebral body without bone metastasis (Figs. 2A, 2B, 2C, and 2D). It is difficult to perform bone SPECT in the cervical vertebrae because their smaller size and more compact structure make localization of the site of uptake difficult [15]. In clinical practice, it might be difficult to distinguish benign from malignant lesions in the vertebrae using SPECT images.
In this study, FDG PET was less sensitive than bone scanning and less sensitive in detecting osteoblastic metastases but more sensitive in detecting osteolytic metastases. These results agree with previously documented findings that FDG PET has a lower sensitivity for detecting breast cancer bone metastases than bone scanning has [10, 11], but FDG PET is superior to bone scanning in the detection of osteolytic breast cancer metastases [6]. The difference between bone scanning and FDG PET for detection of bone metastases in breast cancer is likely related to the difference in the mechanism by which disease is detected by these techniques. Bone scanning detects the osteoblastic response to bone destruction by tumor cells, and FDG PET detects the metabolic activity of the tumor cells [6]. Both osteolytic and osteoblastic processes are important for bone metastases, so FDG PET and bone scanning might be complementary in their ability to detect bone metastases in breast cancer (Figs. 3A, 3B, 3C, 3D, 4A, 4B, and 4C). In this study, 163 bone metastases were diagnosed, consisting of 143 osteoblastic and 20 osteolytic lesions. Therefore, this study shows the low sensitivity of FDG PET in detecting bone metastases in breast cancer when compared with bone scanning. However, FDG PET can rarely detect osteoblastic metastases (Figs. 5A, 5B, and 5C), and bone scanning can rarely detect osteolytic metastases (Figs. 6A, 6B, and 6C).
Among patients with bone metastases from breast cancer, purely osteolytic metastases only might be rare. Our series included no patients with osteolytic metastases only. In previous studies, FDG PET had a lower sensitivity for detecting bone metastases from breast cancer than bone scanning had [10, 11] and a higher number of false-negative FDG PET findings of bone metastases than non-skeletal metastases in breast cancer has been reported [10]. A possible explanation for the apparently poorer results in detecting bone metastases with FDG PET in breast cancer may be the small number of osteolytic metastases: FDG PET showed superiority to bone scanning with osteolytic metastases but failed to detect osteoblastic metastases; on bone scanning, the false-negative rate was only 0.08% in 1,267 consecutive cases of breast cancer [19]. These results might suggest that cases of breast cancer with purely osteolytic metastases only are not common. Therefore, bone scanning will most likely remain the standard radionuclide technique for bone metastases in breast cancer. FDG PET might not be an appropriate initial technique for detecting bone metastases in breast cancer, although FDG PET and bone scanning might be complementary for this purpose.
FDG PET had a great specificity for bone metastases in this study. FDG PET has been reported to have a low false-positive rate for bone metastases in breast cancer [11]. However, no statistically significant difference was observed between FDG PET and bone SPECT with regard to specificity in our study.
One problem of our study is that the existence of bone metastases was determined using the reference methods of MDCT, MRI, and clinical course. Misidentifications of abnormal bone lesions on MDCT or MRI could not be excluded, although clinical follow-up of more than 12 months was used to confirm the final results of analysis of the bone metastases. Our result might not include detection and differentiation of all the osseous lesions that might be revealed at autopsy. However, the histologic confirmation of all osseous lesions is impracticable.
Another problem of our study is that relatively low doses of FDG are injected. If the goal is to detect a small lesion, a larger injected dose may be required. Therefore, our injected doses in the range of 220-240 MBq may reduce the sensitivity of FDG PET. However, in Japan lower injected doses of FDG are typically given because most Japanese patients are smaller than Western patients.
Understanding the advantages and disadvantages of different radionuclide imaging techniques (i.e., FDG PET and bone scanning) in detecting bone metastases will assist the clinician in the screening and treatment planning of breast cancer patients. Routinely performed bone SPECT is practicable and cost-effective and improves the sensitivity of bone scanning.
In conclusion, the detection of osteoblastic lesions is limited on FDG PET. Surveillance of metastatic spread to the skeleton in breast cancer patients based on FDG PET alone is not possible. Bone scanning still remains the most important investigation in the clinical evaluation of skeletal metastases from breast cancer.
Footnote
Address correspondence to T. Uematsu ([email protected]).
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Submitted: June 22, 2004
Accepted: August 10, 2004
First published: November 23, 2012
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