Evaluation of sequential FDG-PET/CT for monitoring bone metastasis of breast cancer during therapy: correlation between morphological and metabolic changes with tumor markers

Purpose

The purpose of this study was to clarify the significance of positron emission tomography (PET) and computed tomography (CT) findings for evaluating the bone metastasis of breast cancer during therapy.

Patients and methods

Forty-seven patients with bone metastases from breast cancer who underwent sequential FDG-PET/CT studies during therapy were enrolled. A total of 771 lesions were identified. The changes in the PET and CT findings were compared with the tumor marker levels in each patient by calculating the weighted kappa value. The correlation between the PET and CT findings was examined for each lesion by an adjusted Chi-square test.

Results

The change in the tumor marker levels was substantially correlated with the PET findings and moderately correlated with the CT findings (weighted kappa?=?0.780 and 0.585 for quadratic weighting, respectively). An increase in FDG uptake was correlated with lytic changes on the CT images (62/65, 95.4?%, p?<?0.05). Sclerotic changes suggested improvement, but sclerosis and progression occurred at the same time in some lesions.

Conclusion

Changes of FDG uptake are useful for evaluating individual bone metastases in cases of breast cancer during therapy. Lytic change on CT images suggests progression of bone metastasis. The lysis-progression/sclerosis-improvement pattern was observed in the majority of subjects, but a sclerosis-progression pattern was also observed. The hybrid pattern of increase of FDG uptake on PET/lytic change on CT is most accurate to show progression of bone metastases. Assessments of these processes during therapy are necessary for the precise evaluation of bone metastases.     

Advantages and limitations of FDG PET in the follow-up of breast cancer

18F-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has been evaluated in breast cancer for the characterisation of primary tumours, lymph node staging and the follow-up of patients after surgery, chemotherapy and/or external radiotherapy. In contrast to both the low sensitivity and moderate specificity of FDG PET in the initial detection and characterisation of breast cancer and the low lesion-based sensitivity for lymph node staging, the results from use of FDG PET in re-staging breast cancer patients are very promising. A major advantage of FDG PET imaging compared with conventional imaging is that it screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of activity, with a reported average sensitivity and specificity of 96% and 77%, respectively. In most studies the sensitivity of FDG PET is higher than that of a combination of conventional imaging methods. Limitations of FDG PET in the follow-up of breast cancer patients include the relatively low detection rate of bone metastases, especially in case of the sclerotic subtype, and the relatively high rate of false positive results. The rather low specificity of FDG PET can be improved/increased by utilising combined anatomical-molecular imaging techniques, such as a PET/CT tomograph. First results using PET/CT imaging in the follow-up of breast cancer patients demonstrate increased specificity compared with FDG PET alone. Both imaging modalities, however, offer to detect recurrent and metastatic breast cancer disease at an early stage and thus continue to demonstrate the efficacy of molecular imaging in patient management, despite the limited therapeutic options in recurrent and metastatic breast cancer.     

FDG-PET and CT patterns of bone metastases and their relationship to previously administered anti-cancer therapy

Purpose To assess ¹⁸F-fluorodeoxyglucose (FDG) uptake in bone metastases in patients with and without previous treatment, and compare positive positron emission tomography (PET) with osteolytic or osteoblastic changes on computed tomography (CT).Methods One hundred and thirty-one FDG-PET/CT studies were reviewed for bone metastases. A total of 294 lesions were found in 76 patients, 81 in untreated patients and 213 in previously treated patients. PET was assessed for abnormal FDG uptake localised by PET/CT to the skeleton. CT was evaluated for bone metastases and for blastic or lytic pattern. The relationship between the presence and pattern of bone metastases on PET and CT, and prior treatment was statistically analysed using the chi-square test.Results PET identified 174 (59%) metastases, while CT detected 280 (95%). FDG-avid metastases included 74/81 (91%) untreated and 100/213 (47%) treated lesions (p<0.001). On CT there were 76/81 (94%) untreated and 204/213 (96%) treated metastases (p NS). In untreated patients, 85% of lesions were seen on both PET and CT (26 blastic, 43 lytic). In treated patients, 53% of lesions were seen only on CT (95 blastic, 18 lytic). Of the osteoblastic metastases, 65/174 (37%) were PET positive and 98/120 (82%), PET negative (p<0.001).Conclusion The results of the present study indicate that when imaging bone metastases, prior treatment can alter the relationship between PET and CT findings. Most untreated bone metastases are PET positive and lytic on CT, while in previously treated patients most lesions are PET negative and blastic on CT. PET and CT therefore appear to be complementary in the assessment of bone metastases.     

18F]fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer

Seventeen patients with advanced breast cancer were imaged with a specially collimated gamma camera to study tumor uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) before and during therapy. Fourteen patients (82%) showed increased FDG accumulation in metastatic tumors, 6/8 (75%) of axillary, supra or infraclavicular metastatic lymph nodes were detectable. In one of these cases, FDG imaging was the first method to identify axillary metastasis causing nerve compression. Also, pulmonary and liver metastases could be imaged with FDG; both in two patients. The intra individual variability in uptake was considerable in bone metastases, and some lesions remained FDG negative: 99mTc-DPD was superior in detecting bone disease. Bone metastases of the osteolytic or mixed type were better visualized than sclerotic ones. Ten patients were reimaged later to assess the effect of therapy on FDG uptake. Increased uptake was associated with clinical progression, while unchanged or diminished uptake did not predict the course of disease as reliably. This study indicates that FDG can be used to image breast cancer metastases. FDG may be valuable in monitoring treatment response, but positron emission tomography (PET) would probably be more appropriate than planar imaging for this purpose.     

Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT

Objective. To characterise the uptake of ¹⁸F in skeletal metastases from breast cancer using positron emission tomography (PET) and to relate these findings to the appearance on CT. Patients and design. PET with ¹⁸F and CT were performed in five patients with multiple skeletal metastases from breast cancer. The CT characteristics were analysed in areas with high uptake on the PET study. Dynamic PET imaging of the skeletal kinetics of the ¹⁸F-fluoride ion were included. Results. The areas of abnormal high accumulation of ¹⁸F correlated well with the pathological appearance on CT. Lytic as well as sclerotic lesions had markedly higher uptake than normal bone, with a 5–10 times higher transport rate constant for trapping of the tracer in the metastatic lesions than in normal bone. Conclusion. PET with ¹⁸F-fluoride demonstrates very high uptake in lytic and sclerotic breast cancer metastases.     

[18F]Fluorodeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer

Seventeen patients with advanced breast cancer were imaged with a specially collimated gamma camera to study tumor uptake of 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) before and during therapy. Fourteen patients (82%) showed increased FDG accumulation in metastatic tumors, 6/8 (75%) of axillary, supra or infraclavicular metastatic lymph nodes were detectable. In one of these cases, FDG imaging was the first method to identify axillary metastasis causing nerve compression. Also, pulmonary and liver metastases could be imaged with FDG; both in two patients. The intra individual variability in uptake was considerable in bone metastases, and some lesions remained FDG negative:^99mTc-DPD was superior in detecting bone disease. Bone metastases of the osteolytic or mixed type were better visualized than sclerotic ones. Ten patients were reimaged later to assess the effect of therapy on FDG uptake. Increased uptake was associated with clinical progression, while unchanged or diminished uptake did not predict the course of disease as reliably. This study indicates that FDG can be used to image breast cancer metastases. FDG may be valuable in monitoring treatment response, but positron emission tomography (PET) would probably be more appropriate than planar imaging for this purpose.     

Positron emission tomography and bone metastases

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?     

Evolving role of positron emission tomography in breast cancer imaging

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used for detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy. FDG uptake in the primary tumor carries prognostic information, but the underlying biochemical mechanisms responsible for enhanced glucose metabolism have not been completely elucidated. Future work using other PET tracers besides FDG will undoubtedly help our understanding of tumor biology and help tailor therapy to individual patient by improving our ability to quantify the therapeutic target, identify drug resistance factors, and measure and predict early response.     

Comparison of fluorodeoxyglucose positron emission tomography and "conventional diagnostic procedures" for the detection of distant metastases in breast cancer patients

The presence of distant metastases is the main prognostic factor in patients with breast cancer and has a significant influence in the choice of therapy. Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are performed to detect distant metastases at diagnosis and follow-up. Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to provide sensitive detection of primary tumour and metastases for many tumour entities, but little information is available about the diagnostic value for breast cancer patients. This study retrospectively compared FDG PET for detection of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the abdomen, referred to as "conventional diagnostic procedures" (CDPs), in 50 breast cancer patients. Imaging procedures were analysed in a blinded fashion with the results classified as "no evidence of metastases", "equivocal" and "evidence of metastases". Clinical follow-up and the results of other imaging modalities including computed tomography and magnetic resonance imaging were used to determine if metastases were present. FDG PET identified metastatic disease with a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs, respectively. Regarding "equivocal" and "evidence of metastases" as positive, the sensitivity of CDPs increased to 57% with a corresponding specificity of 81%, whereas sensitivity and specificity of FDG PET remained unchanged. Regarding different localities of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and especially of lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was of the same magnitude as compared with bone scintigraphy and ultrasound of the abdomen.     

Detection of bone metastases in thyroid cancer patients: bone scintigraphy or 18F-FDG PET?

BACKGROUND: Similar to the situation in other tumour types, it is currently unclear whether fluorodeoxyglucose (FDG) positron emission tomography (PET) is adequate in the detection of bone metastases of thyroid cancer. The purpose of this retrospective study was to evaluate the performance of bone scans in comparison with FDG PET in the detection of bone metastases in patients with differentiated thyroid cancer (DTC). MATERIALS AND METHODS: Twenty-four patients had undergone both FDG PET and bone scans within 6 months because of suspected bone metastases. All scans were re-evaluated using all available additional imaging and clinical data for verification. Scan findings were scored as positive, negative or doubtful. RESULTS: Bone metastases were present in eight of 24 (33%) patients. Only bone scintigraphy but not FDG PET suggested the presence of bone metastases in three patients, all confirmed with magnetic resonance imaging (MRI)/X-ray. Five patients were identified with bone metastases on both bone scan and FDG PET, which was confirmed by computed tomography (CT)/MRI/X-ray in four. Five patients had doubtful findings on bone scans whereas FDG PET scans were negative. MRI showed degenerative disorders in two of five and was normal in two. Eleven patients had both a negative bone scan and FDG PET scan. CONCLUSION: In three of eight (38%) thyroid cancer patients bone metastases were only identified on bone scans. Therefore, bone scans are still valuable in detecting bone metastases in patients with DTC and can not be replaced by FDG PET.     

Usefulness of <Superscript>18</Superscript>F-FDG PET in intrahepatic cholangiocarcinoma

Surgical resection is the only curative treatment strategy for intrahepatic cholangiocarcinoma (CC). Therefore, accurate staging is essential for appropriate management of patients with CC. We assessed the usefulness of 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the staging of CC. We undertook a retrospective review of FDG PET images in 21 patients (10 female, 11 male; mean age 57 years) diagnosed with CC. Ten patients had hilar CC and 11, peripheral CC. Patients underwent abdominal magnetic resonance imaging (MRI) (n=20) and computed tomography (CT) (n=12) for the evaluation of primary tumours, and chest radiography and whole-body bone scintigraphy for work-up of distant metastases. For semi-quantitative analysis, the maximum voxel standardised uptake value (SUV_max) was obtained from the primary tumour. All peripheral CCs showed intensely increased FDG uptake, and some demonstrated ring-shaped uptake corresponding to peripheral rim enhancement on CT and/or MRI. In nine of the ten patients, hilar CCs demonstrated increased FDG uptake of a focal nodular or linear branching appearance. The remaining case was false negative on FDG PET. One patient with a false negative result on MRI demonstrated increased uptake on FDG PET. Among the ten hilar CCs, FDG uptake was intense in only two patients and was slightly higher than that of the hepatic parenchyma in the remaining patients. For the detection of lymph node metastasis, FDG PET and CT/MRI were concordant in 16 patients, and discordant in five (FDG PET was positive in three, and CT and MRI in two). FDG PET identified unsuspected distant metastases in four of the 21 patients; all of these patients had peripheral CC. FDG PET is useful in detecting the primary lesion in both hilar and peripheral CC and is of value in discovering unsuspected distant metastases in patients with peripheral CC. FDG PET could be useful in cases of suspected hilar CC with non-confirmatory biopsy and radiological findings.     

Assessment of malignant skeletal disease: initial experience with 18F-fluoride PET/CT and comparison between 18F-fluoride PET and 18F-fluoride PET/CT.

18F-fluoride PET/CT was performed on 44 oncologic patients to evaluate its diagnostic accuracy in assessing malignant osseous involvement and in differentiating malignant from benign bone lesions. METHODS: (18)F-fluoride PET and (18)F-fluoride PET/CT were interpreted separately. Lesions showing increased (18)F-fluoride uptake were categorized as malignant, benign, or inconclusive. The final diagnosis of lesions was based on histopathology, correlation with contemporaneous diagnostic CT or MRI, or clinical follow-up of at least 6 mo (mean, 10 +/- 3 mo). RESULTS: Increased (18)F-fluoride uptake was detected at 212 sites, including 111 malignant lesions, 89 benign lesions, and 12 lesions for which the final diagnosis could not be determined. In a lesion-based analysis, the sensitivity of PET alone in differentiating benign from malignant bone lesions was 72% when inconclusive lesions were considered false negative and 90% when inconclusive lesions were considered true positive. On PET/CT, 94 of 111 (85%) metastases presented as sites of increased uptake with corresponding lytic or sclerotic changes, and 16 of the 17 remaining metastases showed normal-appearing bone on CT, for an overall sensitivity of 99% for tumor detection. For only 1 metastasis was PET/CT misleading, suggesting the false diagnosis of a benign lesion. The specificity of PET/CT was significantly higher than that of PET alone (97% vs. 72%, P < 0.001). PET/CT identified benign abnormalities at the location exactly corresponding to the scintigraphic increased uptake for 85 of 89 (96%) benign lesions. In a patient-based analysis, the sensitivity of PET and PET/CT was 88% and 100%, respectively (P < 0.05) and the specificity was 56% and 88%, respectively (not statistically significant). Among the 12 patients referred for (18)F-fluoride assessment because of bone pain despite negative findings on (99m)Tc-methylene diphosphonate bone scintigraphy, (18)F-fluoride PET/CT suggested malignant bone involvement in all 4 patients with proven skeletal metastases, a potential benign cause in 4 of 7 patients who had no evidence of metastatic disease, and a soft-tissue tumor mass invading a sacral foramen in 1 patient. CONCLUSION: The results indicate that (18)F-fluoride PET/CT is both sensitive and specific for the detection of lytic and sclerotic malignant lesions. It accurately differentiated malignant from benign bone lesions and possibly assisted in identifying a potential cause for bone pain in oncologic patients. For most lesions, the anatomic data provided by the low-dose CT of the PET/CT study obviates the performance of full-dose diagnostic CT for correlation purposes.     

Whole-body FDG PET/CT is more accurate than conventional imaging for staging primary breast cancer patients

Purpose

This retrospective study aimed (1) to compare the diagnostic accuracy of whole-body FDG PET/CT for initial breast cancer staging with the accuracy of a conventional, multimodal imaging algorithm, and (2) to assess potential alteration in patient management based on the FDG PET/CT findings.

Methods

Patients with primary breast cancer (106 women, mean age 57?±?13?years) underwent whole-body FDG PET/CT and conventional imaging (X-ray mammography, MR mammography, chest plain radiography, bone scintigraphy and breast, axillary and liver ultrasonography). The diagnostic accuracies of FDG PET/CT and a conventional algorithm were compared. Diagnostic accuracy was assessed in terms of primary tumour detection rate, correct assessment of primary lesion focality, T stage and the detection rates for lymph node and distant metastases. Histopathology, imaging or clinical follow-up served as the standards of reference.

Results

FDG PET/CT was significantly more accurate for detecting axillary lymph node and distant metastases (p?=?0.0125 and p?Conclusion Full-dose, intravenous contrast-enhanced FDG PET/CT was more accurate than conventional imaging for initial breast cancer staging due to the higher detection rate of metastases and synchronous tumours, although the study had several limitations including a retrospective design, a possible selection bias and a relevant false-positive rate for the detection of axillary lymph node metastases. FDG PET/CT resulted in a change of treatment in a substantial proportion of patients.     

F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging

AIM: To evaluate the role of F-18-fluorodeoxyglucose positron-emission tomography (F-18 FDG PET) in the follow-up of breast carcinoma in case of clinical suspicion of local recurrence or distant metastases and/or tumor marker increase in correlation to conventional imaging. MATERIAL AND METHODS: Retrospective analysis of the results of F-18 FDG PET (ECAT ART(R), Siemens CTI MS) of 62 patients (age 58.5 +/- 12.8) with surgically resected breast carcinoma (time interval after surgery, 86 +/- 82 months, mean follow-up 24 +/- 12.6 months). Patient- and lesion-based comparison with conventional imaging (CI) including mammography (MG), ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI), radiography (XR) and bone scintigraphy (BS). Furthermore, we evaluated the influence on tumor stage and therapeutic strategy. A visual qualitative evaluation of lesions was performed. RESULTS: On a patient base, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detecting local recurrence or distant metastases were calculated to be 97%, 82%, 87%, 96% and 90% compared with 84%, 60%, 73%, 75% and 74% with CI. On a lesion base, significantly more lymph node (84 vs. 23, P < 0.05) and fewer bone metastases (61 vs. 97, P < 0.05) could be detected by using F-18 FDG PET compared with CI. Sclerotic bone lesions were predominantly detected by BS. On the other hand, there were several patients with more FDG positive bone lesions and also mixed FDG positive/Tc-99m methylenediphosphonate (MDP) negative and FDG negative/Tc-99m MDP positive metastases. In case of normal tumor markers, sensitivity, specificity, PPV, NPV and accuracy for detecting local recurrence or distant metastases were calculated to be 100%, 85.0%, 78.6%, 100% and 90.3% for FDG PET and 80%, 50%, 50%, 80% and 61.5% for CI. An upstaging could be observed in 9.7% (6/62) and downstaging in 12.9% (8/62), leading to a change in therapeutic regimen in 13 patients (21%). CONCLUSIONS: F-18 FDG PET demonstrates apparent advantages in the diagnosis of metastases in patients with breast carcinoma, compared with conventional imaging on a patient base. On a lesion base, significantly more lymph node and less bone metastases can be detected by using F-18 FDG PET compared with conventional imaging, including bone scintigraphy. In patients with clinical suspicion but negative tumor marker profile, too, F-18 FDG PET seems to be a reliable imaging tool for detection of tumor recurrence or metastases. Considering the high predictive value of F-18 FDG PET, tumor stage and therapeutic strategy will be reconsidered in several patients.     

Comparison of bone scintigraphy and 18F-FDG PET-CT in a prostate cancer patient with osteolytic bone metastases

A 62?year-old male with prostate cancer, recently complaining lumbar pain with elevated PSA level (6.83?ng/ml) was referred for evaluating bone metastases. Bone scintigraphy with (99m)Tc-MDP demonstrated intense uptake on third lumbar vertebra. Postoperative biopsy of the lesion on third lumbar vertebra revealed adenocarcinoma metastasis. For evaluating distant metastases and restaging, (18)F-FDG PET-CT was performed postoperatively. On PET-CT imaging there were cervical and left parailiac lymph nodes with FDG uptake, destruction on third lumbar vertebra level and intense soft tissue mass FDG uptake on the same area. Additionally, FDG uptake was detected on right iliac crest. On the CT images obtained by integrated PET-CT scanner, this uptake was matching with lytic bone metastases. The superiority of (18)F-FDG PET-CT for demonstrating osteolytic bone metastases compared to bone scintigraphy was presented in a case of prostate cancer in a patient with bone and lymph node metastases.     

Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose

The authors assessed whether breast cancers can be detected by means of positron emission tomography (PET) with the positron-emitter-labeled glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). In 12 patients with primary and/or metastatic breast cancer, PET images of F-18 distribution in vivo were obtained approximately 1 hour after intravenous injection of 10 mCi of FDG. Scan findings were correlated with other imaging data and physical examination and biopsy results. Ten of 10 primary breast cancers were imaged by means of FDG PET with a tumor:background FDG uptake ratio of 8.1 (median). Ten of 10 bone metastases were imaged with a tumor:normal bone uptake ratio of 6.05 (median). Five of five known soft-tissue metastases and four previously unsuspected nodal lesions were found with PET. No false-positive foci of FDG uptake were demonstrated. In two cases with negative mammograms due to dense breast parenchyma, FDG PET clearly delineated the primary tumors. These preliminary data demonstrate the feasibility and substantial potential of PET scanning with FDG to detect and localize both primary and metastatic breast cancers.     

Current and future uses of positron emission tomography in breast cancer imaging

Positron emission tomography using ¹⁸F-fluorodeoxyglucose (FDG-PET) has been used for the detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy. FDG uptake in the primary tumor carries prognostic information, but the underlying biochemical mechanisms that are responsible for enhanced glucose metabolism have not been completely elucidated. Future work using other PET tracers besides FDG will undoubtedly help our understanding of tumor biology, improve our ability to measure and predict response and help tailor therapy to individual patients.     

High-risk melanoma: accuracy of FDG PET/CT with added CT morphologic information for detection of metastases

PURPOSE: To prospectively determine the accuracy of positron emission tomography (PET)/computed tomography (CT) with added CT morphologic information for depiction of metastases in patients with high-risk melanoma and negative findings for metastases at PET, by using histologic findings or additional imaging and/or follow-up findings as reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained. Informed consent was obtained from patients. One hundred twenty-four consecutive high-risk melanoma patients (65 female, 59 male; mean age, 54.4 years; range, 15-82 years) were included. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT was performed. First, PET/CT scans were evaluated for presence of metastases with increased FDG uptake; CT anatomic location was determined. Lesions were considered metastases if there was focal uptake higher than that of background tissue. Second, coregistered CT images of combined PET/CT scans were evaluated for presence of lesions without FDG uptake. Findings were compared with reference standard findings to determine the accuracy of each evaluation. McNemar test was used to assess statistical differences in accuracy. RESULTS: In 53 of 124 patients, metastases were found. In 46 of 53 patients with metastases, lesions had increased FDG uptake. In seven patients with metastatic disease, metastases did not have increased FDG uptake (maximum standard uptake value [SUV], <1.5; n = 5) or had faint FDG uptake (maximum SUV, 2.5 and 2.9; n = 2)-findings that were inconclusive with PET alone. These lesions were interpreted as metastases only with coregistered CT images. Lesions missed with PET were located in the lungs, iliac lymph nodes, subcutis, and psoas muscle. Sensitivity, specificity, and accuracy, respectively, of PET/CT for depiction of metastases were 85%, 96%, and 91%, and those of PET/CT with dedicated CT interpretation were 98%, 94%, and 96% (P = .016). CONCLUSION: Dedicated analysis of coregistered CT images significantly improves the accuracy of integrated PET/CT for depiction of metastases in patients with high-risk melanoma.     

The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast

Diagnostic imaging has played a major role in the evaluation of patients with bone metastases. The imaging modalities have included bone scintigraphy, computed tomography, magnetic resonance imaging, and most recently PET/CT, which can be performed with different tracers, including fluorodeoxyglucose (FDG), 18F-fluoride, 18F-choline (FCH), and 18F-DOPA (dihydroxyphenylalanine). For most tumors the sensitivity of FDG in detecting bone metastases is similar to bone scintigraphy; additionally it can be used to monitor the response to chemotherapy and hormonal therapy. 18F-Fluoride may provide a more sensitive "conventional" bone scan and is superior for FDG nonavid tumors, but, nevertheless, FDG in "early disease" often has clear advantages over 18F-fluoride. Although more data need to be obtained, it appears that FCH is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented. For neuroendocrine tumors and in particular in medullary thyroid cancer, DOPA is similar to 18F-fluoride in providing high quality information regarding the skeleton. Nevertheless, prospective studies with large patient groups will be essential to define the exact diagnostic role of FCH and DOPA PET in different clinical settings.     

Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer

Purpose The purpose of this study was to investigate the pitfalls of using 2-[¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the evaluation of osteoblastic bone metastases in patients with breast cancer by comparing it with ^99mTc-hydroxymethylene diphosphonate bone scintigraphy.Methods Among the 89 breast cancer patients (mean age 59±15 years) who had undergone both FDG-PET and bone scintigraphy within 1 month between September 2003 and December 2004, 55 with bone metastases were studied. The bone metastases were visually classified by multi-slice CT into four types according to their degree of osteosclerosis and osteolysis—osteoblastic, osteolytic, mixed and invisible—and compared in terms of tracer uptake on FDG-PET or bone scintigraphy and SUV_mean on FDG-PET. Differences in the rate of detection on bone scintigraphy and FDG-PET were analysed for significance by the McNemar test.Results The sensitivity, specificity and accuracy of bone scintigraphy were 78.2%, 82.4% and 79.8% respectively, and those of FDG-PET were 80.0%, 88.2% and 83.1%, respectively, revealing no significant differences. According to the CT image type, the visualisation rate of bone scintigraphy/FDG-PET was 100%/55.6% for the blastic type, 70.0%/100.0% for the lytic type, 84.2%/94.7% for the mixed type and 25.0%/87.5% for the invisible type. The visualisation rates of bone scintigraphy for the blastic type and FDG-PET for the invisible type were significantly higher. The SUV_mean of the blastic, lytic, mixed and invisible types were 1.72±0.28, 4.14±2.20, 2.97±1.98 and 2.25±0.80, respectively, showing that the SUV_mean tended to be higher for the lytic type than for the blastic type.Conclusion FDG-PET showed a low visualisation rate in respect of osteoblastic bone metastases. Although FDG-PET is useful for detection of bone metastases from breast cancer, it is apparent that it suffers from some limitations in depicting metastases of the osteoblastic type.An editorial commentary on this paper is available at