The role of computed tomography in the detection of bone metastases in breast cancer patients

Computed tomography (CT) of bone was carried out in 20 patients with breast cancer, all of whom had abnormal radionuclide uptake on skeletal scintigrams but normal conventional radiographs. Twenty-eight sites were examined and 13 showed metastases in 11 patients. Five of these patients had no evidence of extra-skeletal recurrent disease. Follow-up at eight of these sites showed healing, sclerosis or progression, all of which correlated well with clinical findings. CT showed benign causes of radionuclide accumulation in three patients (7 sites) but no abnormality in six patients (8 sites). None of these patients has subsequently developed bone metastases. CT is superior to conventional radiographs in the diagnosis of skeletal metastases and should be carried out when skeletal scintigraphy is positive and conventional examinations are normal.     

Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19–39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14–22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.     

Diagnostic value of MRI in comparison to scintigraphy, PET, MS-CT and PET/CT for the detection of metastases of bone

The initial localization of metastases in the bone in patients with solid tumors has a relatively good prognosis in comparison with visceral metastasization. The early detection of bone marrow metastases allows for a rapid initiation of therapy and a subsequent reduction in the morbidity rate. Modern MRI is superior to the 30-year-old skeletal scintigraphy and bone marrow scintigraphy with respect to sensitivity, specificity, as well as the extent of osteal metastasis. MRI provides substantial, therapy-relevant additional information. MSCT plays an important role in the management of cancer patients in clinical routine and gives an excellent survey of the axial skeleton by demonstrating osteolytic and osteoblastic metastases. Extensive comparative studies of MRI with 18F-FDG-PET and 18F-fluoride-PET have not yet been carried out. Whole body MRI is a very promising new staging method for the oncological diagnosis of solid tumors and the detection of osteal metastases. The adoption of 18F-FDG-PET and 18F-fluoride-PET FDG as well as the side by side PET-CT image fusion and the two in one PET/CT examinations appears to be slightly less sensitive to whole body MRI in the detection of osteal metastases. Larger, prospective multicenter studies are necessary to establish these as new, promising methods for the detection of osteal metastases.     

Observations on the sequential use of Tc-99m phosphonate and Ga-67 imaging in untreated primary and secondary malignant tumors of the head and neck

Scintigraphy using both Tc-99m phosphonate and Ga-67 was performed in 55 cases of untreated primary and secondary tumors of the head and neck. In 21 patients with primary tumors of jaws, eye, tongue, or parotid gland, Ga-67 scintigraphy visualized the primary tumor in all cases and metastases in 12. Scintigraphy using Tc-99m phosphonate disclosed primary bone involvement in 12 cases and skeletal metastases in two. In eight of 13 patients with metastatic lesions of jaws and skull, bone scintigraphy showed skeletal metastases. In seven of these patients, Ga-67 scintigraphy detected the primary tumor and in 11 cases detected metastases. Bone scintigraphy disclosed skeletal metastases in six of 21 patients with malignant neck tumors. In 13 of these patients, Ga-67 scintigraphy visualized the primary tumor, whereas it showed metastases in seven. It is concluded that Ga-67 scintigraphy should be used in the investigation of untreated primary or secondary malignant tumors of the head and neck. Bone scintigraphy may be indicated as an additional study in selected cases only.     

The usefulnes of99mTc-HMPAO-labeled leukocyte scintigraphy in the diagnosis of skeletal metastases of cancers

The usefulness of bone marrow scintigraphy with 99mTc-HMPAO-labeled leukocytes (leukocyte bone marrow scintigraphy) in the diagnosis of skeletal metastases of cancers was investigated in 70 lesions in 27 patients with various types of cancer. The final diagnosis of skeletal metastases was based on one or more criteria consisting of histological confirmation, typical findings of metastases by bone radiograph, CT and MRI, or progressive swellings of the lesions with severe pain due to nerve compression. Of the 70 lesions, 55 were finally diagnosed as metastases, and 15 as benign lesions. Leukocyte bone marrow scintigraphy showed photopenic defects in 52 of the 55 metastatic lesions (sensitivity 95%), and the remaining 3 negative lesions were found positive for metastases by MRI. In contrast, MRI could evaluate only 39 of the 55 lesions because 16 lesions in the ribs, scapula and sternum were not visualized. Of these 39 lesions, MRI showed positive findings for metastases in 33 (sensitivity 85%), and negative findings in 6 with photopenic defects found by leukocyte bone marrow scintigraphy. Of the 15 benign lesions, 3 were false positive for metastases on leukocyte bone marrow scintigraphy (specificity 80%). We conclude that 99mTc-HMPAO-labeled leukocyte bone marrow scintigraphy may be useful in the diagnosis of skeletal metastases of cancers, particularly when MRI fails to evaluate the lesions.     

Frequency of skeletal metastases in nasopharyngeal carcinoma after initiation of therapy: should bone scans be used for follow-up?

Previous reports have indicated a relatively high incidence of distant metastases in patients with nasopharyngeal carcinoma (NPC), one of the most common sites being the skeleton. Although bone scintigraphy offers the advantage of whole-body imaging in patients with cancer by providing useful information about disease spread, its value in patients with NPC is not well defined because of cost-effectiveness considerations. In this study, we assessed the value of follow-up bone scintigraphy for the evaluation of skeletal metastases in patients with different stages of NPC. Between 1994 and 2001, 230 patients with histologically proven NPC were admitted to the Department of Radiation Oncology. Out of 230 patients, 171 were examined for skeletal metastases with bone scintigraphy prior to therapy and at 1 year intervals. Bone scintigraphy detected increased uptake in 29 patients, which was reported as suggestive of metastases or equivocal. Twenty-six of these were true-positive, confirmed by radiography or clinical follow-up. Bone pain was present in 67% of these patients and serum lactate dehydrogenase and alkaline phosphatase were elevated in 35% and 37%, respectively. The incidence of bone metastases correlated with the extent of lymph node involvement, which were detected after a median time of 10.5 months following the diagnosis of the primary disease. No correlation was observed between the metastatic status and local T stage, histological differentiation age or gender of the patient. We can therefore recommend that bone scintigraphy be used in determining the presence of bone metastases, but its utilization should be preserved for those with nodal involvement.     

Bone scintigraphy in testicular tumors

PURPOSE: Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade. MATERIALS AND METHODS: The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy. RESULTS: The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases. DISCUSSION: Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic. CONCLUSIONS: Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis.     

Role of whole-body diffusion-weighted MRI in detecting bone metastasis

Purpose

The aim of this study was to compare the results of whole-body diffusion-weighted magnetic resonance (DW-MR) imaging with staging based on computed tomography (CT) and nuclear scintigraphy using Tc99m results as the standard of reference.

Methods and materials

Seventeen patients with known malignant tumours were included in the study. The thorax and the abdomen were imaged using breath-hold diffusion-weighted imaging and T1-weighted imaging sequences in the coronal plane. Location and size of osseous metastases were documented by two experienced radiologists. Whole-body DW-MR imaging findings were compared with results obtained at skeletal scintigraphy and CT bone survey.

Results

The mean examination time for whole-body DW-MR imaging was 25.5 min. All bone metastases regardless of the size were identified with whole-body DW-MR imaging; MR imaging depicted more bone metastases than CT. Skeletal scintigraphy depicted osseous metastases in 13 patients (with greater sensitivity to the lower limb), whereas whole-body DW-MR imaging revealed osseous metastases in 13 patients (with greater sensitivity to the spine). DW-MR did not show good results for detection of rib cage metastases. The additional osseous metastases seen with MR imaging were confirmed at follow-up examinations and some had a change in therapy. MR identified 22 % more metastatic lesions when compared to bone scintigraphy and 119 % when compared to CT. Bone scintigraphy identified 80 % more metastatic lesions when compared to CT. On a per-patient basis, whole-body DW-MR imaging revealed sensitivity and specificity values of 100 %.

Conclusion

Whole-body DW-MR imaging was more sensitive in the detection of osseous metastases than were skeletal scintigraphy and CT bone survey.     

Fast spin echo MRI and bone scintigraphy in the detection of skeletal metastases

Standard Spin Echo (SE) magnetic resonance imaging (MRI) is known to be a very sensitive method for the detection of bone metastases and in comparison to skeletal scintigraphy, MRI detects more lesions when field of view includes the area of suspicion. However, only with the introduction of new fast SE sequences, have MRI protocols, for the detection of metastases, become rapid enough to make it a potential screening procedure for metastatic disease. Twenty-one patients with a suspicion of carcinomatous bone metastases were evaluated with both conventional T1 weighted (T1w), T2 weighted (T2w) and fast T2w SE (FSE) sequences (thoraco-lumbar spine and pelvis) and whole body bone scintigraphy. Conventional and fast T2w SE sequences detected the same number of lesions while bone scintigraphy detected only 70% of the lesions seen on MRI. However, more importantly, in 11 of the 21 patients bone scintigraphy detected lesions outside the MR field of view, lying in the ribs, skull, scapulae and extremities and in 4 of them, MRI was negative. Our results suggest first that fast SE MRI can replace conventional SE MRI when looking for carcinomatous bone metastases in the axial skeleton, with the advantage of a four to six times reduced acquisition time for fast T2w sequences. However, the limited field of view still limits the usefulness of MRI and whole body bone scintigraphy remains the screening modality for bone metastases. Fast MRI plays an important complementary role. Correspondence to: G. K. von Schulthess     

99mTc-MIBI scintigraphy in untreated stage III multiple myeloma: comparison with X-ray skeletal survey and bone scintigraphy

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) is a lipophilic agent that has been proposed as a useful tracer for the detection of disease sites in patients with multiple myeloma (MM). We performed a prospective study to determine the potential of 99mTc-MIBI imaging for the evaluation of the extent of primary disease in patients with advanced stage MM, compared with skeletal survey and bone scintigraphy. Twenty patients with advanced stage MM at initial diagnosis underwent whole-body 99mTc-MIBI imaging, together with contemporaneous skeletal survey and bone scintigraphy. The findings of 99mTc-MIBI imaging were correlated with the results of skeletal survey and bone scan. All 99mTc-MIBI scans were positive for the presence of active MM, whereas skeletal surveys were positive in 18 patients (90%) with osteolytic lesions. Bone scintigraphy demonstrated MM in only 15 patients (75%). In two patients with no detectable lesions on skeletal survey, 99mTc-MIBI imaging revealed uptake in the spine, corresponding to the abnormalities seen on magnetic resonance imaging (MRI). With respect to the localization of bone lesions, 99mTc-MIBI imaging was superior to bone scintigraphy in 15 patients (75%) and had concordant results with bone scintigraphy in four (20%). 99mTc-MIBI imaging is a very sensitive imaging modality for the identification of the extent of disease in patients with advanced MM. It is clearly superior to bone scintigraphy and complements the results of skeletal survey by finding additional disease sites. Hence, in active MM patients, 99mTc-MIBI imaging has the potential to detect bone marrow disease that cannot be detected by skeletal survey and bone scintigraphy.     

The role of bone scintigraphy in osteogenic sarcoma

Hospital records of 27 children with osteogenic sarcoma were reviewed in an effort to define the usefulness of skeletal scintigraphy in the initial evaluation and follow-up of their disease. Serial bone scans as well as plain radiographs, linear tomograms, and computed tomograms were evaluated for evidence of bone or lung metastases. Eighteen patients developed lung metastases and three developed bone metastases. Seven patients demonstrated uptake of tracer in lung metastases, however, the lesions were all easily identifiable by radiographic means. All bone metastases were detected by scintigraphy, in one instance prior to radiographic abnormality. In no cases were bone metastases known to occur in the absence of lung metastases. None of the bone scans performed for routine follow-up pruposes resulted in altered therapy for the patient. We propose that skeletal scintigraphy is useful in the initial metastatic work up of osteogenic sarcoma, and may be helpful in some patients with specific indications during their follow-up, but is less valuable when there is no clinical suspicion for bone metastases.     

Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of whole-body MR imaging, skeletal scintigraphy, and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for the detection of bone metastases in children. SUBJECTS AND METHODS: Thirty-nine children and young adults who were 2--19 years old and who had Ewing's sarcoma, osteosarcoma, lymphoma, rhabdomyosarcoma, melanoma, and Langerhans' cell histiocytosis underwent whole-body spin-echo MR imaging, skeletal scintigraphy, and FDG PET for the initial staging of bone marrow metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference. RESULTS: Twenty-one patients exhibited 51 bone metastases. Sensitivities for the detection of bone metastases were 90% for FDG PET, 82% for whole-body MR imaging, and 71% for skeletal scintigraphy; these data were significantly different (p < 0.05). False-negative lesions were different for the three imaging modalities, mainly depending on lesion location. Most false-positive lesions were diagnosed using FDG PET. CONCLUSION: Whole-body MR imaging has a higher sensitivity than skeletal scintigraphy for the detection of bone marrow metastases but a lower sensitivity than FDG PET.     

The value of non-staging skeletal scintigraphy in breast cancer

A series of 315 patients with histologically proven breast cancer had skeletal scintigraphy performed for defined reasons other than initial staging. Of these, 173 (55%) were found to be abnormal. The yield of abnormalities was highest (83%) in patients with bone pain or tenderness and radiographic evidence of metastases: 38% in those with bone pain or tenderness alone, 37% in asymptomatic patients with local or regional recurrence and 54% in those with non-bony metastases. The overall actuarial survival over a maximum follow-up of 9 years was significantly worse for those with abnormal scintigraphy. Non-staging skeletal scintigraphy is useful in detecting asymptomatic bone metastases at the time of local or regional recurrence or in the presence of non-bony metastases.     

Role of skeletal scintigraphy in advanced retinoblastomas

PURPOSE: To document the incidence of skeletal metastases exclusively in advanced cases of retinoblastoma and to rationalize the use of preoperative skeletal scintigraphy in such patients. MATERIAL AND METHODS: Preoperative bone scans of 36 consecutive patients with advanced retinoblastoma who underwent skeletal scintigraphy during 1998 to 2003 were analyzed retrospectively. Bone scans were classified as: Grade 1 (high probability scan for skeletal metastases), Grade 2 (equivocal malignant or benign abnormalities), or Grade 3 (normal or certainly benign lesions). RESULTS: Grade 1 scan was found in 3 (8.33%) patients; bone metastases were confirmed by additional investigations. Grade 2 scan was found in 5 (13.88%) patients; bone metastases were excluded in all by additional investigations. Grade 3 scan was found in the remaining 28 (77.77%) patients. Extraorbital extension of disease was demonstrated by fine needle aspiration of lymph nodes in five patients, which included all three patients with Grade 1 scan. In addition to lymph node metastases, two patients had intracranial extension of the disease; demonstrated by contrast-enhanced magnetic resonance imaging of the head. One patient had liver metastases detected on abdominal ultrasound. None of the patients had skeletal metastases only. CONCLUSION: Routine preoperative bone scan is not justified in patients with locally advanced retinoblastoma. Bone scan should only be performed in patients with documented extraocular metastatic disease.     

Staging bone scintigraphy in nasopharyngeal carcinoma

Bone scintigraphy was performed on 163 new cases of nasopharyngeal carcinoma without clinical evidence of distant metastases. Among the 10 abnormal bone scans one patient had radiographic skeletal metastases corresponding to the areas of increased tracer uptake. Two patients with abnormal bone scans subsequently developed radiographic metastases at the site of abnormal tracer uptake. The detection rate of asymptomatic skeletal metastases on presentation was thus 1.8% (3/163), and the predictive value of an abnormal scan for metastases 30% (3/10). Bone scintigraphy is not justified as a routine staging investigation for nasopharyngeal carcinoma, although it can be considered for a subset of patients considered at high risk of distant metastases.     

Value of whole-body turbo short tau inversion recovery magnetic resonance imaging with panoramic table for detecting bone metastases: comparison with 99MTc-methylene diphosphonate scintigraphy

OBJECTIVE: The objectives of this study were to assess the efficacy and reliability of whole-body turbo short tau inversion recovery (STIR) magnetic resonance imaging (MRI) for detecting skeletal metastasis and to compare the results with those of bone scintigraphy. METHODS: Twenty-six patients with primary cancer (mean age=56 years, age range: 34-75 years) were assessed for bone metastasis with whole-body MRI and bone scintigraphy. Eight bone regions in each patient were assessed (total of 208 sites) with each of these 2 techniques. A turbo STIR sequence and panoramic table were used during MRI. Whole-body MRI and scintigraphy findings were compared with biopsy or follow-up imaging results. RESULTS: After at least 12 months of follow-up, 9 patients had bone metastases in a total of 31 sites. Whole-body MRI showed 29 metastases (94%) in the total 208 skeletal sites investigated in the 26 patients. Bone scintigraphy revealed metastases in 16 (52%) of the 208 sites. CONCLUSION: Whole-body turbo STIR MRI is a reliable method for screening patients with suspected skeletal metastases. This technique is also advantageous in that it reveals extraskeletal organ and soft tissue metastases.     

Detection of bone marrow metastases by FDG-PET and missed by bone scintigraphy in widespread melanoma

The optimal management of patients with melanoma requires accurate imaging techniques that can screen the entire body for metastases. One of the most used tests for this purpose is bone scintigraphy. PET has been reported to be more sensitive than bone scintigraphy in some malignancies. In our case, FDG-PET was also superior to bone scintigraphy in detecting the extent of skeletal disease in a patient with melanoma. This is likely the result of the fact that metastasis to bone marrow may not result in bone reaction in certain conditions and therefore bone scans may remain negative despite skeletal involvement.     

Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient

Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq ^99mTc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of ±20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within ±19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.     

Synthesis of trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid and its radiolabelling with 99mTc for the detection of skeletal metastases

BACKGROUND AND AIM: The development of bone-seeking radiopharmaceuticals for the detection of malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. This study aimed to provide a convenient synthesis of trans-1,2-cyclohexylenedinitrilo tetramethylene phosphonic acid (CDTMP) and an improved preparation of its (99m)Tc complex. METHODS: CDTMP was prepared from trans-1,2-cyclohexyldinitrilotetraacetic acid by reaction with phosphorus trichloride and it was labelled with (99m)Tc. Toxicity and biodistribution studies were carried out in BALB/c mice, while blood clearance and bone scintigraphy studies were carried out in rabbits. (99m)Tc-CDTMP was evaluated for the detection of malignant bone lesions in 11 patients. Bone scintigraphy (a methylene diphosphonate scan) was performed to detect metastases at diagnosis and follow-up. RESULTS: The radiolabelling efficiency was found to be >97% and the stability in serum indicated that (99m)Tc remained bound to the chelate, CDTMP, for up to 24 h. Blood clearance showed a quick wash-out from the circulation and the biological half-lives (t12) were 55 min (F) and 8 h 48 min (S). The LD50 was 110 mg.kg(-1) as determined by toxicity studies. The drug was excreted mainly through renal route and the accumulation of (99m)Tc-CDTMP in bone was 7.69+/-0.65%ID/g at 1 h. The mean ratio of bone lesion to soft tissue was 6.8+/-0.69 and of bone lesion to normal bone was 5.67+/-0.82. Visual image analysis of (99m)Tc-CDTMP was clinically comparable to the interpretation of imaging studies with (99m)Tc-MDP. CONCLUSION: These preliminary data support increased bone uptake by the tetraphosphonate complex of (99m)Tc. This suggests that CDTMP complexed with therapeutic radionuclides should be evaluated for therapy of skeletal metastases.     

False negative bone scans in neuroblastoma metastatic to the ends of long bones.

Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup.