Christiane Franzius

FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy

Abstract. The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewings sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6–64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewings sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewings sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewings sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.

Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis.

Purpose The purpose of this study was to evaluate the potential of positron emission tomography using F-18-fluoro-2-deoxy-D-glucose (FDG PET) to assess the chemotherapy response of primary osseous tumors compared with the degree of necrosis determined histologically. Patients and Methods Seventeen patients with primary bone tumors (11 osteosarcomas, 6 Ewing’s sarcomas) were examined using FDG PET and planar bone scintigraphy before neoadjuvant chemotherapy and before surgery. Tumor response was classified histologically according to Salzer-Kuntschik (grades I–III: good response; grades IV–VI: poor response). In both imaging methods, quantification was performed using tumor to nontumor ratios (T:NT). Results Histologically, 15 patients were classified as having good responses (grade I, n = 1; grade II, n = 6; grade III, n = 8) and two as having poor responses (grades IV and V). FDG PET showed more than a 30% decrease in T:NT ratios in all patients who had good responses. However, three of these patients had increasing bone scintigraphy T:NT ratios, and another five had decreasing ratios of less than 30%. The patients with poor responses had increasing T:NT ratios and decreasing ratios of less than 30%, respectively, using both imaging methods. Conclusions FDG PET seems to be a promising tool for evaluating the response of primary osseous tumors to chemotherapy. In this preliminary study, FDG PET was superior to planar bone scintigraphy.

[18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group

PURPOSE In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM). PATIENTS AND METHODS A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT. RESULTS Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET. CONCLUSION The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.

Significant Benefit of Multimodal Imaging: PET/CT Compared with PET Alone in Staging and Follow-up of Patients with Ewing Tumors

Hybrid PET/CT was compared with PET alone in the staging and restaging of patients with Ewing tumor to assess the benefit of the combined imaging technique. Methods: A total of 163 18F-FDG PET/CT studies performed in 53 patients (age: range, 4–38 y; median, 16.5 y) with histopathologically confirmed Ewing tumor were evaluated retrospectively. All PET/CT studies included low-dose CT for attenuation correction; in 91 examinations, additional diagnostic chest CT was performed. PET and CT data were assessed independently by 2 nuclear medicine physicians and 2 radiologists, respectively. Finally, both datasets were fused by use of software and analyzed by all 4 reviewers (consensus reading). Each lesion was scored with a 5-point scale. Biopsy, imaging, or clinical follow-up served as a standard of reference. Receiver operating characteristic (ROC) analyses were performed to evaluate PET and PET/CT performance characteristics. To measure the abilities to detect and correctly localize tumor foci, localization ROC (L-ROC) curves were generated for PET. Results: A total of 609 lesions were detected by PET alone. The hybrid PET/CT technique resulted in a change of score in 160 of these lesions (26%): higher scores in 23 lesions (4%) and lower scores in 137 lesions (23%). In 49 lesions detected by PET (8%), the localization had to be changed after image fusion. Additionally, 124 (21%) more lesions were found by PET/CT than by PET alone, resulting in a total of 733 lesions. As determined by lesion-based analysis, the sensitivity, specificity, and accuracy of PET were 71%, 95%, and 88%, respectively; the corresponding values for the hybrid PET/CT technique were 87%, 97%, and 94% (P < 0.0001). The areas under the curve in the ROC analysis were 0.82 for PET and 0.92 for PET/CT (P < 0.0001), and that in the L-ROC analysis was 0.66 for PET. Conclusion: PET/CT is significantly more accurate than PET alone for the detection and localization of lesions and improves staging for patients with Ewing tumor. The hybrid technique is superior to PET alone in terms of sensitivity, specificity, and accuracy, mainly because of the detection of new lesions.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.MethodsFDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.ResultsFDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (∆SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (∆SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.ConclusionFDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

[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.

Staging in childhood lymphoma Differences between FDG-PET and CT

AIM The clinical value of positron emission tomography using fluorine-18 fluoro-deoxy-glucose (FDG-PET) in the staging of adult lymphoma has been shown in many studies. However, there are only few data regarding childhood lymphoma. The purpose of this retrospective study was to compare the staging of childhood lymphoma using FDG-PET and the established computed tomography (CT). METHOD Whole-body FDG-PET was performed in 25 children with histologically proven Hodgkins disease (n = 18) and non-Hodgkins lymphoma (n = 7) using a dedicated PET. The findings were compared with the CT results. Both examinations, FDG-PET and CT, were assessed by two experienced physicians. In each patient, 30 regions were analysed (22 nodal, 8 extranodal). Each region was assessed using a five value scale (definitely/probably positive, equivocal, probably/definitely negative). RESULTS 662 regions (470 nodal, 192 extranodal) were compared. 91 regions (81 nodal, 10 extranodal; 14%) were concordant positive and 517 regions (347 nodal, 170 extranodal; 78%) were concordant negative. In 47 regions, 48 discordant findings (7%) were described: 27 findings (22 nodal, 5 extranodal) were positive using FDG-PET and negative using CT whereas 21 findings (17 nodal, 4 extranodal) were positive using CT and negative using PET. A total of 7 regions (1%) were judged equivocal in one imaging modality (1 FDG-PET, 6 CT). Using FDG-PET as compared to CT, resulted in a higher staging in 4 of 25 patients and in a lower staging in 2 of 25 patients. CONCLUSION Staging of childhood lymphoma using FDGPET shows differences compared with CT resulting in a different staging in 6 of 25 patients. Prospective studies are required to evaluate the impact of these discrepancies on the clinical management of pediatric patients.

Determination of extent and activity with radionuclide imaging in Erdheim-Chester disease.

Erdheim-Chester disease usually involves the diaphyseal and metaphyseal regions of tubular bones and various visceral organs. A 56-year-old woman presented with the histologically confirmed diagnosis of Erdheim-Chester disease. A Tc-99m MDP bone scan revealed the entire extent of the skeletal disease and showed unusual involvement of the epiphyses and axial skeleton. In addition to MRI, a Ga-67 citrate scan including SPECT showed extensive soft-tissue infiltration of different organs. Both Tc-99m MDP and Ga-67 scintigraphy are useful tools in determining the distribution of this rare disease.

Is PET/CT necessary in paediatric oncology?

In principle, there are two different strategies of using the CT component in PET/CT [15]. On the one hand, a CT scan with low radiation exposure can be performed for the purpose of attenuation correction of the PET data (so-called low-dose CT). This low-dose CT can additionally be used for anatomical orientation, which is a major advantage in comparison to PET performed as a single modality. Recently, clinically significant incidental findings from the dose-reduced unenhanced CT portion have been reported [16]. However, the diagnostic impact of the CT data acquired using minimised tube current–time product (e.g. 13–20 mAs), which is sufficient for attenuation correction within a PET/CT scan, needs to be evaluated in further investigations. On the other hand, a CT scan obtained as part of PET/CT can meet the quality level of a diagnostic CT scan [15, 17, 18]. In this setting, CT has to be performed with adequate tube current–time product and tube voltage, usually following intravenous administration of iodinated contrast medium and, in the case of abdominal CT, oral contrast medium. Furthermore, the CT protocol can be adapted to the clinical question with a mixture of both, e.g. combining a diagnostic CT of the neck and chest with a low-dose CT of the abdomen and pelvis. Our own experience with 356 paediatric patients demonstrates a learning curve. There has been an increasing acceptance by the referring paediatricians of the diagnostic potential of the CT component and the hardware fusion technique. PET/CT was performed with a diagnostic CT of at least one part of the body in 40% of the first 100 patients scanned. A diagnostic CT was carried out in 49% of the second 100 patients, in 59% of the third 100 patients and in 71% of the most recent 56 patients. The increasing number of diagnostic CT scans is due to performance of the necessary and indicated diagnostic CT scans within the PET/CT examination instead of performing two single examinations, a diagnostic CT scan and a PET scan.

Kinetic parameters of 3-[123I]iodo-L-α-methyl tyrosine ([123I]IMT) transport in human GOS3 glioma cells

Abstract The radiolabelled amino acid 3-[ 123 I]iodo-L-α-methyl tyrosine ([ 123 I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [ 123 I]IMT uptake in human glioma cells. The kinetic analysis of [ 123 I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent Michaelis constant (K m = 20.1 ± 1.5 μM). The maximum transport velocity (V max ) amounted to 34.8 ± 1.9 nmol/mg protein/10 min. Competitive inhibition experiments revealed that [ 123 I]IMT transport is mediated principally by the sodium-independent system L.