Joachim Sciuk

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.

FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: Comparison with spiral CT

BACKGROUND The purpose was the comparison of positron emission tomography using F-18-fluorodeoxy-glucose (FDG-PET) and spiral thoracic CT to detect pulmonary metastases from malignant primary osseous tumors. PATIENTS AND METHODS In 71 patients with histologically confirmed malignant primary bone tumors (32 osteosarcomas, 39 Ewings sarcomas) 111 FDG-PET examinations were evaluated with regard to pulmonary/pleural metastases in comparison with spiral thoracic CT. Reference methods were the clinical follow-ups for 6-64 months (median 20 months) or a histopathologic analysis. RESULTS In 16 patients (23%) reference methods revealed a pulmonary/pleural metastatic disease. FDG-PET had a sensitivity of 0.50, a specificity of 0.98, and an accuracy of 0.87 on a patient based analysis. Comparable values for spiral CT were 0.75, 1.00, and 0.94. It was shown that no patient who had a true positive FDG-PET had a false negative CT scan, nor was a pulmonary metastases detected earlier by FDG-PET than by spiral CT. CONCLUSIONS There seems to be a superiority of spiral CT in the detection of pulmonary metastases from malignant primary bone tumors as compared with FDG-PET. Therefore, at present a negative FDG-PET cannot be recommended to exclude lung metastases. However, as specificity of FDG-PET is high, a positive FDG-PET result can be used to confirm abnormalities seen on thoracic CT scans as metastatic.

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.

Comparison of technetium 99m polyclonal human immunoglobulin and technetium 99m monoclonal antibodies for imaging chronic osteomyelitis. First clinical results.

The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.

Benzodiazepine receptors and cerebral blood flow in partial epilepsy

It was the aim of this study to compare benzodiazepine (Bz) receptor binding and cerebral perfusion in patients with partial epilepsy. Single photon emission tomography (SPET) studies with the flow-marker technetium 99m hexamethylpropylene amine oxine (99mTc-HMPAO) and with the 123I-labelled Bz-receptor ligand Ro 16-0154 (123I-Iomazenil) were performed in 12 patients with partial epilepsy, all with normal magnetic resonance imaging (MRI) and computed tomography (CT) scans. The SPET studies with 123I-Iomazenil were carried out 5 min and 2 h after injection. At 2 h the distribution of activity was very similar to the expected distribution of Bz-receptors in the human brain, known from positron emission tomography (PET) work and post-mortem studies. Early images showed a significantly higher tracer accumulation in the area of the basal ganglia, cerebellum, and naso-pharyngeal space. This finding is caused by non-specific binding and the contribution of the tracer in the blood pool in this phase. Also after 2 h p.i. of 123I-Iomazenil, 9 of the 12 patients showed a focal decrease of of Bz-receptor binding. Ten patients had focal flow abnormalities with 99mTc-HMPAO SPET. In 8 subjects impairment of flow was seen in sites of reduced 123I-Iomazenil uptake. 123I-Io-mazenil is suitable for Bz-receptor mapping. In this series of patients, Bz-receptor mapping with SPET seems to offer no advantage over 99mTc-HMPAO in the detection of epileptic foci.

White blood cell scintigraphy with monoclonal antibodies in the study of the infected endoprosthesis.

Forty-three patients with suspected infection of a hip or a knee prosthesis were studied with white blood cell scintigraphy (WBC), using technetium-99m (n = 37) or iodine-123 (n = 6) labelled monoclonal mouse antibody (MoAb). Previously, all patients had undergone skeletal scintigraphy, which was performed as a three-phase study in 33 cases. The final diagnosis was established by open surgery, histology and culture in 37 cases, by puncture and culture in 3 cases, and by clinical follow-up of at least 6 months in 3 cases. Eighteen prostheses were infected, 25 uninfected. The delayed phase of skeletal scintigraphy had a sensitivity of 92%, a specificity of 24% and an accuracy of 48% in the detection of infection. The perfusion and blood pool activity of the three-phase bone scan had a sensitivity of 67%, a specificity of 71% and an accuracy of 70%. The diagnostic value of WBC was sensitivity 89%, specificity 84% and accuracy 86%. WBC with 99m-Tc-MoAb is easy to perform and always available. Its diagnostic accuracy is similar to conventional WBC scintigraphy with either indium-111 or technetium-99m.

Intraoperative, probe-guided curettage of osteoid osteoma.

The only curative approach for osteoid osteoma is operative removal of the nidus, but intraoperative detection of the nidus is difficult even when an X-ray amplifier is used. A simple probe-guided operative procedure using technetium-99m methylene diphosphonate is described, and the results and follow-up in 12 patients are reported. In addition physical properties of the probe have been evaluated by phantom measurements.

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.

N-(2-diethylaminoethyl)-4-[123I]iodobenzamide as a tracer for the detection of malignant melanoma: simple synthesis, improved labelling technique and first clinical results.

In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.

Characterization of 3-[123I]iodo-L-α-methyl tyrosine ([123I]IMT) transport into human Ewing’s sarcoma cells in vitro

3-[(123)I]Iodo-L-alpha-methyl tyrosine ([(123)I]IMT) scintigraphy of extracranial malignant tumors has been described, but little is known about the transport systems involved in [(123)I]IMT uptake into extracranial tumor cells. Here, the precise kinetics of [(123)I]IMT transport into human Ewings sarcoma cells (VH-64) was determined. The apparent Michaelis constant was of high affinity value (K(m)=41.7+/-3.9 microM) and maximum transport velocitiy amounted to V(max)=20.7+/-0.6 nmol x mg protein(-1) x 10 min(-1). Inhibition experiments revealed the predominance of [(123)I]IMT uptake via sodium-independent system L.