[Bone scanning with sodium 18F-fluoride PET and PET/CT. German guideline Version 1.0.]. / Skelettdiagnostik mittels 18F-Natriumfluorid-PET und -PET/CT. DGN-Leitlinie Version 1.0.

In nuclear medicine, bone scanning is based on the principle of scintigraphy using bone-seeking radiopharmaceuticals which accumulate in sites of increased bone formation. From a historical point of view, (18)F-fluoride was one of the first osteotropic tracers which was replaced by (99m)Tc-labelled polyphosphonates. With the development of modern PET equipment the superior diagnostic performance of (18)F-fluoride PET for the detection and characterization of osseous lesions was proven in comparison to conventional bone scanning. Recently, its importance as a substitute of conventional skeletal scintigraphy increased in a time with limited availability of (99)Mo/(99m)Tc. To ensure health care during this period, (18)F-fluoride PET currently became part of common outpatient care. This guideline comprehends recommendations on indications, protocols, interpretation and reporting of (18)F-fluoride PET and PET/CT.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography.

PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18-PET and conventional BS. F-18-PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca(2+), alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methods was used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18-PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18-PET imaging, clinical management was changed in four patients (11.7%). For F-18-PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P <.05) and 1.00 on a patient basis (for BS, it was 0.82; P <.05). CONCLUSION: F-18-PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer.

UNLABELLED: Previous studies have shown that vertebral bone metastases (BM) not seen on planar bone scintigraphy (BS) might be present on (18)F-fluoride PET scans or at MRI. Therefore, we evaluated the effect of SPECT or (18)F-labeled NaF PET ((18)F PET) imaging on the management of patients with newly diagnosed lung cancer. METHODS: Fifty-three patients with small cell lung cancer or locally advanced non-small cell lung cancer were prospectively examined with planar BS, SPECT of the vertebral column, and (18)F PET. MRI and all available imaging methods, as well as the clinical course, were used as reference methods. BS with and without SPECT and (18)F PET were compared using a 5-point scale for receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve patients had BM. BS produced 6 false-negatives, SPECT produced 1 false-negative, and (18)F PET produced no false-negatives. The area under the ROC curve was 0.779 for BS, 0.944 for SPECT, and 0.993 for (18)F PET. The areas under the ROC curve of (18)F PET and BS complemented by SPECT were not significantly different, and both tomographic methods were significantly more accurate than planar BS. As a result of SPECT or (18)F PET imaging, clinical management was changed in 5 patients (9%) or 6 patients (11%), respectively. CONCLUSION: As indicated by the area under the ROC curve analysis, (18)F PET is the most accurate whole-body imaging modality for screening for BM. Routinely performed SPECT imaging is practicable, is cost-effective, and improves the accuracy of BS.

Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET.

UNLABELLED: Radionuclide bone scanning (RNB) is considered to be the most practical screening technique for assessing the entire skeleton for skeletal metastases. However, RNB has been shown to be of lower sensitivity than MRI and CT in detecting osteolytic metastases. A prospective study was designed to evaluate the accuracy of planar RNB versus tomographic bone imaging with 18F-labeled NaF and PET (18F PET) in detecting osteolytic and osteoblastic metastases and its dependency on their anatomic localization. METHODS: Forty-four patients with known prostate, lung or thyroid carcinoma were examined with both planar RNB and 18F PET. A panel of reference methods including MRI of the spine, 1311 scintigraphy, conventional radiography and spiral CT was used as the gold standard. RNB and 18F PET were compared by a lesion-by-lesion analysis using a five-point score for receiver operating characteristic (ROC) curve analysis. RESULTS: 18F PET showed 96 metastases (67 of prostate carcinoma and 29 of lung or thyroid cancer), whereas RNB revealed 46 metastases (33 of prostate carcinoma and 13 of lung or thyroid cancer). All lesions found with RNB were also detected with 18F PET. Compared with 18F PET and the reference methods, RNB had a sensitivity of 82.8% in detecting malignant and benign osseous lesions in the skull, thorax and extremities and a sensitivity of 40% in the spine and pelvis. The area under the ROC curve was 0.99 for 18F PET and 0.64 for RNB. CONCLUSION: 18F PET is more sensitive than RNB in detecting osseous lesions. With RNB, sensitivity in detecting osseous metastases is highly dependent on anatomic localization of these lesions, whereas detection rates of osteoblastic and osteolytic metastases are similar. Higher detection rates and more accurate differentiation between benign and malignant lesions with 18F PET suggest the use of 18F PET when possible.

Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity?

UNLABELLED: PET with 18F-FDG has been shown to be useful in the detection and staging of pancreatic cancer. However, whether FDG uptake is dependent on proliferative activity is still unclear. The aim of this prospective study was to evaluate a probable correlation between FDG uptake and proliferative activity in benign and malignant pancreatic tumors. METHODS: Our series consisted of 23 patients with pancreatic cancer and 9 patients with chronic active pancreatitis (CAP). FDG PET was performed within 2 wk before surgery, and standardized uptake values (SUVs) were calculated for benign and malignant pancreatic tumors. Patients were selected when focally increased FDG uptake in previously known pancreatic tumors was present. Proliferation fraction was measured in tissue specimens using the anti-Ki-67 antibody MIB-1. A computer-assisted imaging system was used for quantification of nuclear Ki-67 immunostaining. Immunohistochemical findings were correlated to SUVS: RESULTS: Pancreatic cancer showed both intense nuclear staining of Ki-67 (39% +/- 16%) and high FDG uptake (SUV = 3.6 +/- 1.6). However, no significant correlation was found between in vivo FDG uptake and Ki-67 immunoreactivity (P = 0.65). By contrast, Ki-67 nuclear staining was significantly lower (3.8% +/- 2.7%, P < 0.05) in CAP, whereas FDG uptake was in the same range as for pancreatic cancer (SUV = 3.5 +/- 1.8). CONCLUSION: FDG uptake did not correlate with proliferative activity in pancreatic cancer. Proliferative activity was tenfold higher in malignant pancreatic tumors than in benign tumors associated with CAP, whereas FDG uptake in vivo did not differ significantly. Thus, a PET tracer indicating cellular proliferation should better differentiate between cancer and inflammatory lesions than do metabolic markers such as FDG.

[18F] 3-deoxy-3'-fluorothymidine positron emission tomography: alternative or diagnostic adjunct to 2-[18f]-fluoro-2-deoxy-D-glucose positron emission tomography in the workup of suspicious central focal lesions?

BACKGROUND: 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography has been established as a standard diagnostic imaging method in the preoperative workup of suspicious pulmonary focal lesions, showing a sensitivity of more than 90% and a specificity of about 80%. Determination of malignant pulmonary lesions with FDG positron emission tomography depends on the assessment of glucose metabolism. However, false-positive findings can occur in inflammatory processes, such as sarcoidosis or pneumonia. The thymidine analogue 3-deoxy-3[(18)F]-fluorothymidine (FLT) is a new positron emission tomography tracer that more specifically targets proliferative activity of malignant lesions. The objective of this study was to determine whether FLT positron emission tomography, in comparison with FDG positron emission tomography, provides additional information in the preoperative workup of central pulmonary focal lesions. METHODS: In this prospective study FLT and FDG positron emission tomography examinations were performed as a part of the preoperative workup in 20 patients with histologically confirmed bronchial carcinoma, 7 patients with benign lesions, and 1 patient with an atypical carcinoid. Results were compared with final pathologic findings. RESULTS: For staging of the primary tumor, FLT positron emission tomography revealed a sensitivity of 86% and a specificity of 100% compared with a sensitivity of 95% and a specificity of 73% for FDG positron emission tomography. For N staging, the sensitivity of FLT positron emission tomography was 57% and the specificity was 100%, and for FDG positron emission tomography, the sensitivity was 86% and the specificity was 100%, respectively. CONCLUSIONS: Our preliminary findings indicate specific FLT uptake in malignant lesions. The number of false-positive findings in FDG positron emission tomography might be reduced with FLT positron emission tomography. Therefore positron emission tomography imaging with FLT represents a useful supplement to FDG in assessing the malignancy of central pulmonary focal lesions.

Positron emission tomography for detection and staging of malignant lymphoma.

FDG-Positron emission tomography (FDG-PET) is an imaging modality using the physiological tracer glucose [modified as 18-fluorine-2-fluorodeoxyglucose (FDG)], whose uptake and metabolism is increased in malignant cells. While exact tumor staging in lymphomatous diseases is the basis for choosing the appropriate treatment strategy, the detection of nodal and extranodal manifestations are a key prerequisite. This study demonstrates that FDG-PET is an efficient, non-invasive method for the staging of primary untreated Hodgkin's lymphoma (HD) and non-Hodgkin's lymphoma (NHL). Clinical PET scanning is very useful in staging lymphoma patients and is more accurate than computed tomography (CT) in detecting lesions.

Anatomical distribution and sclerotic activity of bone metastases from thyroid cancer assessed with F-18 sodium fluoride positron emission tomography.

Currently, bone scintigraphy (BS) is considered to lack sensitivity in detecting bone metastases (BM) from thyroid cancer. We evaluated the anatomical distribution and metabolic behavior of BM as well as the accuracy of BS with and without combination of whole-body iodine scintigraphy (WBI) in detecting metastatic bone disease in thyroid carcinoma. F-18 positron emission tomography (PET), x-ray, BS, and WBI were performed in 35 patients with known or suspected bone metastases from papillary (9 patients) or follicular (26 patients) thyroid carcinoma. Twenty-two metastases were previously known in 14 patients. The indication was staging in 21 patients with high risk for BM, elevated thyroglobulin (Tg)-levels or evaluation of exact extent of BM (14 patients). In addition, results of WBI (35 patients), X-ray (35 patients) F-18 PET (35 patients), MRI of the spine (13 patients), and FDG-PET (15 patients) as well as the clinical course (1.5-4 years) were correlated. BM were detected in 18 patients. Solitary, bifocal, or multiple lesions were present in 9, 2, and 7 patients, respectively. The anatomical distribution of BM (n = 43) was as follows: spine, 42%; skull, 2%; thorax, 16%; femur, 9%; pelvis, 26%; humerus and clavicle, 5%. Sensitivity of BS in interpreting patients as positive or negative for having BM was 64%-85% (specificity, 95%-81%). The combination of BS and WBI was 100% sensitive in detecting metastatic bone disease. One patient had a single BM that was positive at BS but negative on WBI. All metastases were osteolytic on x-ray and two-thirds presented a missing or very limited osteosclerotic bone reaction on F-18 PET. Our data confirm the limited sensitivity of planar BS in detecting BM from thyroid cancer. The combination of BS and WBI, however, was highly accurate. Compared to other malignancies, the distribution pattern of BM presented a lower percentage of vertebral metastases and more patients with single metastases. Those findings in combination with a missing or only slight osteosclerotic bone reaction explain the limited sensitivity of planar BS alone.

Sentinel-node biopsy for axillary staging in breast cancer: results from a large prospective German multi-institutional trial.

PURPOSE: To analyse the reliability of sentinel-node biopsy (SNB) in a multicentre setting and define conditions for the routine use of the procedure. MATERIAL AND METHODS: SNB with consecutive axillary clearing was performed in 1124 breast cancer patients. The detection rate of a sentinel lymph node and its dependence on the choice of lymphography technique, patient selection, and technical procedure were analysed. The diagnostic performance of the sentinel-node method was compared to clinical, ultrasound-guided and histological staging. In order to study training effects all learning periods were included. RESULTS: Twenty-two institutions with a total of 89 surgeons participated in the trial. The detection rate (overall: 85.2%) was found to be related to the applied lymphography technique, the experience of the institution and various technical factors of the procedure itself. The false-negative rate (FNR, overall: 8.2%) was independent of patient selection and technical features. The FNR did not depend on experience in the application of the method, but seemed related to surgical accuracy to detect sentinel nodes. Compared to conventional staging procedures (palpation, ultrasound) SNB yielded highly reproducible results for the prediction of the axillary status even in a multicentre setting involving surgeons with different training status. CONCLUSION: SNB is suited as standard of care procedure. Measures of quality control appear more important than learning periods to minimize the FNR.

Is (18)F-fluorodeoxyglucose positron emission tomography in recurrent colorectal cancer a contribution to surgical decision making?

BACKGROUND: Accuracy of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contribution to surgical decision making in recurrent or metastatic colorectal cancer were evaluated. METHODS: One hundred whole-body PET tests in colorectal cancer patients (1994 to 1998) were compared with computed tomography (CT), liver ultrasonography, and carcinoembryonic antigen (CEA) test. Mean follow-up was 12 months. RESULTS: Sensitivity, specificity, and accuracy of FDG-PET for malignant findings were, respectively, 98%, 90% and 95%; for 87 CT scans, 91%, 72%, and 82%; for 98 CEA tests, 76%, 90%, and 82%; for detection of liver metastases with PET, 100%, 99%, and 99%; and for 68 ultrasound tests, 87%, 96%, and 93%. PET accuracy for local recurrence was 96%. Additional information was provided by PET in 86% of cases (abdomen, thorax, liver). PET influenced surgical decisions in 61% of cases. CONCLUSION: FDG-PET adds relevant accuracy to the conventional staging of patients with colorectal cancer and may cost-effectively help to select the appropriate treatment.

Pre-operative staging of invasive breast cancer with MR mammography and/or PET: boon or bunk?

This study compared pre-operative staging with MR mammography (MRM) and positron emission tomography (PET) in patients with clinically suspected breast cancer according to the Breast Imaging Reporting and Data System, category 5. A total of 43 patients with breast cancer were examined. MRM included both T(2) weighted turbo spin echo sequences and T(1) weighted gradient echo sequences (three-dimensional fast low angle shot) before and after application of gadolinium-DPTA. All patients then underwent examination with a modern full-ring PET scanner following injection of fluorodeoxyglucose. We evaluated the efficacy of these methods in the diagnosis of primary tumour, contralateral carcinomas, bifocal, trifocal or multifocal disease, as well as non-invasive cancer portions and tumour size. Determination of patients' N-status was only attempted using PET. All findings were validated by histological examination. MRM was slightly superior to PET in several areas, such as in the respective methods' sensitivity and specificity. Sensitivities for MRM and PET were: 100% vs 93.0% in diagnosis of the primary tumour; 100% vs 100% in diagnosis of contralateral carcinomas; and 95.2% vs 92.5% in diagnosis of bifocal, trifocal or multifocal disease. Specificities for MRM and PET were: 100% vs 97.5% in diagnosis of contralateral carcinomas; and 96.8% vs 90.3% in diagnosis of bifocal, trifocal or multifocal disease. Non-invasive cancer portions and tumour sizes were equally well determined with both methods. The sensitivity of PET for detection of lymph node involvement was 80% and specificity 95%. MRM and PET were superior to conventional methods in nearly all areas studied; the findings of one or both of the methods impacted positively on patients' surgical treatment in 12.5-15% of cases. Pre-operative MRM and/or PET can have a positive influence on surgical treatment planning. Therefore, it appears useful to perform pre-operative staging with MRM or PET in these patients.

[Imaging of the normal skeletal system with 18F Na-PET compared with conventional skeletal scintigraphy using Tc99m-MDP]. / Darstellung des normalen Skelett-systems mit 18FNa-PET im Vergleich zur konventionellen Skelettszintigraphie mit 99mTc-MDP.

PURPOSE: We evaluated the feasibility of 18 Fluoride Positron Emission Tomography (18F-PET), investigated the characteristics appearance of bony structures, and compared the quality of 18F-PET images with conventional bone scans (BS). METHOD: 18F-PET scans were performed in 59 patients additional to conventional bone scintigraphy. RESULTS: Even very small details in the spine like the spinous and transverse processes were clearly visible with 18F-PET. Only half of these structures were visualised with BS. When visualising the vertebral bodies of the first rib from the clavicles and the twelfth rib from the kidneys, we arrived at similar results. Hot spots in the skull or at the manubriosternal joint were observed in 29% of the patients without any evidence of trauma, degeneration or metastasis. CONCLUSION: 18F-PET shows more details of the skeleton compared to BS. Some hot spots not occurring with BS must be regarded as physiological.

[Positron-emission tomography of the skeletal system using 18FNa: the incidence, pattern of the findings and distribution of benign changes]. / Die Positronenemissionstomographie des Skelettsystems mit 18FNa: Häufigkeit, Befundmuster und Verteilung benigner Veränderungen.

PURPOSE: We evaluated the frequency, distribution and appearance of benign lesions in 18F-PET scans. METHODS: Between March 1996 and May 1997, 18F-PET scans were performed in 59 patients in addition to conventional planar bone scintigraphy. Eleven patients were subjected to additional SPECT imaging. The main indication was searching for bone metastases (58 pat.). The diagnosis was confirmed radiologically. RESULTS: With 18F-PET in 39 patients (66.1%) 152 benign lesions, mostly located in the spine were detected. 99mTc bone scans revealed 45 lesions in 10 patients. Osteoarthritis of the intervertebral articulations (69%) or of the acromioclavicular joint (15%) were the most common reasons for degenerative lesions detected with 18F-PET. Osteophytes appeared as hot lesions located at two adjacent vertebral endplates. Osteoarthritis of the intervertebral articulations showed an enhanced tracer uptake at these localizations, whereas endplate fractures of the vertebral bodies appeared very typical; solitary fractures of the ribs could not be differentiated from metastases. Rare benign lesions were not studied. CONCLUSION: Most of the degenerative lesions (84%) detected with 18F-PET had a very typical appearance and could be detected with the improved spatial resolution and advantages of a tomographic technique. 18F-PET had an increased accuracy in detecting degenerative bone lesions.

[F-18-FDG PET for primary diagnosis differential diagnosis of pleural processes]. / F-18-FDG-PET zur Primärdiagnostik und Dignitätsbeurteilung pleuraler Prozesse.

PURPOSE: Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) has been shown to be accurate for differentiating benign from malignant pulmonary lesions. Therefore, we evaluated the capability of FDG-PET in the characterisation of pleural lesions. PATIENTS AND METHODS: PET was performed in thirteen patients with pleural or intrapulmonal tumors (three with additional pleural effusion) and in three patients with aetiologically unclear pleural effusion demonstrated by CT. In all cases the diagnosis was confirmed histologically. The PET-imaging was carried out in fasted patients 50 minutes after injection of 400-670 MBq F-18-FDG without attenuation correction. RESULTS: Twelve patients were found to have pleural or pulmonal malignomas (9 pleural mesotheliomas, 3 bronchogenic adenocarcinoma with carcinomatous pleurisy). Four patients had benign pleural changes (1 fibroma, 1 tuberculous pleurisy, 1 pleural fibrosis, 1 empyema). With FDG-PET, all 12 pleural or intrapulmonal malignomas had high FDG-uptake and were classified correctly. Due to very low or virtually deficient FDG-uptake, four histologically benign lesions were correctly interpreted as nonmalignant. CONCLUSION: These preliminary results suggest that FDG-PET is accurate in detecting malignant pleural tumors.

[Sentinel node biopsy in breast cancer]. / Wächterlymphknotenbiopsie beim Mammakarzinom.

The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.