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G Glatting

Publications and source records attributed to G Glatting.

At least 19 recordsLinked to original sources

[Advancement of PET and PET/CT in prostate carcinoma].

Functional imaging of prostate carcinoma was examined with the metabolic substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F-fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F-choline is preferentially incorporated into phosphatidylcholine of membrane lipids of prostate cancer cells. PET allows sensitive detection of the (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic signal localisation. Most published studies report a high detection rate of prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate carcinoma from benign hyperplasia and from focal chronic prostatitis may be difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity comparable to prostate carcinoma.

Carbon Radioisotopes↗

[PET and PET/CT in relapsing prostate carcinoma].

Of patients with carcinoma of the prostate undergoing therapeutic regimes with curative intent, 15-23% will ultimately relapse and 16-35% will need some sort of salvage therapy within 5 years. Of relapsing patients, 50% will have local recurrence and 50% systemic disease with or without local recurrence. Therefore, localization of recurrent prostate cancer is critical for selecting a local or systemic therapeutic strategy. Modern fusion imaging with PET/CT and 11C/18F-choline or 11C-acetate has augmented the diagnostic imaging spectrum for assessment of relapsing prostate cancer. In 60-70% of patients with biochemical relapse, recurrent tumor can be detected and anatomically precisely localized. Detection sensitivity is probably negatively correlated with serum PSA concentration. Below a PSA level of 1 ng/ml, mean detection sensitivity is probably 50-66%. Fusion imaging with 11C-choline PET/CT and MRI possesses a high potential for early localization of recurrent prostate carcinoma.

Humans↗

Dosimetry with (188)Re-labelled monoclonal anti-CD66 antibodies. A simplified approach based on a single measurement 3 h p.i.

AIM: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a (188)Re-labelled anti-CD66 monoclonal antibody. PATIENTS, METHODS: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 +/- 12 years) the residence times were determined for the injected (188)Re-labelled anti-CD66 antibodies (1.3 +/- 0.4 GBq, 5-7 GBq/mg protein, >95% (188)Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. RESULTS: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 +/- 0.2 h, 1.9 +/- 0.8 h, 7.8 +/- 2.1 h, 0.6 +/- 0.3 h and 8.6 +/- 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. CONCLUSION: The proposed approach allows reliable prediction of biokinetics of (188)Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

Antibodies, Monoclonal↗

Internal radionuclide therapy: software for treatment planning using tomographic data.

AIM: Accurate dosimetry must be performed for each patient before therapy with unsealed radionuclides. Recently, the software tool ULMDOS was developed to facilitate planar dosimetric calculations and to support traceability and documentation as a prerequisite for good clinical practice. Here, the extended version of ULMDOS for processing of tomographic data is presented. METHODS: ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. Serial tomographic data can be loaded in an ECAT7 or DICOM format, and presented as maximum intensity projection. The definition of volumes of interest is supported by various tools (e.g., freehand, isocontour, polygon), region growing, and cluster analysis. Residence times are calculated from fits of the time activity data to exponential functions. RESULTS, DISCUSSION: Quantitative 3-dimensional data allow performing a more individualized dosimetry, as problems due to organ overlay, insufficient attenuation and scatter correction in the planar approach can be avoided. For traceability, documentation, retrospective examination and later processing all data can be saved in binary or ASCII format. Dosimetric calculations can be conducted within a single environment, thus it spares the time-consuming transfer of data between different software tools.

Humans↗

[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.

Adenocarcinoma↗

[Significance of PET for ENT-tumors].

Significance for ENT-tumors. Molecular imaging with PET is based on the use of specific radioactive molecules as source of image contrast. In ENT-tumors mostly glucose and occasionally amino acid/protein metabolism were assessed with PET for tumor diagnosis. Thymidine salvage pathway and proliferation as well as tissue hypoxia are tested already in clinical studies and bear considerable potential for modulation of radiation ports and therapeutic response of cytoreductive regimens. This short review summarises actual clinical indications and potential of PET in ENT-tumors. For both nodal staging as well as detection of recurrent disease, sensitivity and specifity of FDG-PET were 80 - 100 %. FDG-PET proved to be superior to conventional imaging in most published studies. In CUP-syndrome the primary could be detected in 25 - 50 % of patients. Acquisition of PET and CT images in a combined scanner allow versatile PET based metabolic imaging in combination with high resolution and anatomical precise CT-based morphological imaging and thus combines advantages of both imaging modalities. Clinical as well as scientific potential of this functional metabolic and high resolution morphological imaging approach is high.

Amino Acids↗

Lymph node staging in lung cancer using [18F]FDG-PET.

BACKGROUND: Mediastinal lymph node staging is essential to determine treatment options in patients with NSCLC. Positron emission tomography (PET) detects increased glucose uptake in malignant tissue using the glucose analogue 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS: In the present study were evaluated 155 patients with focal pulmonary tumors who underwent both preoperative computed tomography (CT) and FDG-PET scanning (116 malignant and 39 benign lesions). RESULTS: Findings in 155 patients included 116 malignant and 39 benign lesions. For N-staging, FDG-PET showed a sensitivity of 88%, a specificity of 91%, and an accuracy of 89%. Corresponding figures for CT were 77%, 76%, and 77%, respectively. CONCLUSIONS: FDG-PET is an effective, noninvasive method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to operability, FDG-PET could differentiate reliable between patients with N1/N2 disease and those with unresectable N3 disease.

Adenocarcinoma↗

Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer.

UNLABELLED: In a pilot trial we investigated whether significant differences in prostate cancer (PCA) imaging would be observed using [(11)C]acetate and [(11)C]choline positron emission tomography (PET). METHODS: Twelve patients were studied with both radiotracers. Whole body PET without attenuation correction was performed after injection of 0.95 +/- 0.15 GBq [(11)C]acetate and 0.84 +/- 0.13 GBq [(11)C]choline, respectively, from 5 to 60 min p. i. Focally increased uptake in bone, below the urinary bladder or in a lymph node region was considered as tumour. Primary tumour, lymph node involvement, bone metastases, local recurrence; and no evidence of disease were known in 2, 4, 2, 2; and 2 patients, respectively. RESULTS: [(11)C]Acetate uptake was highest in spleen and pancreas while [(11)C]choline uptake was predominant in liver and kidney parenchyma. However, interindividual variation was high. The potential of both radiotracers to detect known bone lesions, lymph node metastases, and imaging of the primary tumour was identical. However, both failed to detect a small local recurrence in two patients as well as to demonstrate lymph node involvement in one patient, which was confirmed by surgery. CONCLUSIONS: In this preliminary study, uptake of both radiotracers in prostate cancer or its metastases was nearly identical and none of them should be favoured. At present, both radiotracers influence patient management by detection of local recurrence, lymph node, or bone metastases of PCA.

Acetates↗

Simultaneous iterative reconstruction of emission and attenuation images in positron emission tomography from emission data only.

For quantitative image reconstruction in positron emission tomography attenuation correction is mandatory. In case that no data are available for the calculation of the attenuation correction factors one can try to determine them from the emission data alone. However, it is not clear if the information content is sufficient to yield an adequate attenuation correction together with a satisfactory activity distribution. Therefore, we determined the log likelihood distribution for a thorax phantom depending on the choice of attenuation and activity pixel values to measure the crosstalk between both. In addition an iterative image reconstruction (one-dimensional Newton-type algorithm with a maximum likelihood estimator), which simultaneously reconstructs the images of the activity distribution and the attenuation coefficients is used to demonstrate the problems and possibilities of such a reconstruction. As result we show that for a change of the log likelihood in the range of statistical noise, the associated change in the activity value of a structure is between 6% and 263%. In addition, we show that it is not possible to choose the best maximum on the basis of the log likelihood when a regularization is used, because the coupling between different structures mediated by the (smoothing) regularization prevents an adequate solution due to crosstalk. We conclude that taking into account the attenuation information in the emission data improves the performance of image reconstruction with respect to the bias of the activities, however, the reconstruction still is not quantitative.

Algorithms↗

[Implementation of a measurement protocol to evaluate system parameters in positron emission tomography].

To evaluate system parameters in PET measurements, several different activity ratios of the investigated phantom must be analyzed. The aim of this study was to develop a measurement protocol which requires just one filling of the phantom to measure adequate image contrasts and count ranges. We used 11C for the hollow spheres and 18F for the background of the whole-body PET phantom. Because of the different half-lives of the radionuclides, the dynamic acquisition of the frames (duration compensated for 18F decay) realizes various activity ratios between the spheres and the constant background. By summing up different frames, the counts in the background can also be varied. The presented method reduces the radiation exposure of the staff and economizes the use of the tomograph.

Carbon Radioisotopes↗

[Assessment of image reconstruction parameters in PET using physical and statistical figures of merit].

The aim of this study was to analyze the recommended OSEM image reconstruction parameters in positron emission tomography (PET). Spatial resolution, signal-to-noise ratio, and contrast were used as physical figures of merit (FOM). For statistical FOMs, the t-value and the area under the receiver operating characteristic (ROC) were employed. The spatial resolution was measured with 21 point sources. The signal-to-noise ratio, the contrast, and the t-value were investigated with a whole-body phantom with hollow spheres inserted. A phantom containing line sources was used for ROC analysis. As result, the reconstruction parameters recommended for visual evaluation lead to images with an adequate lesion detectability. The quantitative reconstruction, however, needs improvement.

Artifacts↗

Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study.

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n = 15) or an alternative donor (n = 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

Acute Disease↗

In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model.

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.

Animals↗

2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial.

BACKGROUND: The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG-PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients.

Adolescent↗

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures.

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

Adult↗

Validation of myocardial blood flow estimation with nitrogen-13 ammonia PET by the argon inert gas technique in humans.

We simultaneously determined global myocardial blood flow (MBF) by the argon inert gas technique and by nitrogen-13 ammonia positron emission tomography (PET) to validate PET-derived MBF values in humans. A total of 19 patients were investigated at rest (n = 19) and during adenosine-induced hyperaemia (n = 16). Regional coronary artery stenoses were ruled out by angiography. The argon inert gas method uses the difference of arterial and coronary sinus argon concentrations during inhalation of a mixture of 75% argon and 25% oxygen to estimate global MBF. It can be considered as valid as the microspheres technique, which, however, cannot be applied in humans. Dynamic PET was performed after injection of 0.8 +/- 0.2 GBq 13N-ammonia and MBF was calculated applying a two-tissue compartment model. MBF values derived from the argon method at rest and during the hyperaemic state were 1.03 +/- 0.24 ml min-1 g-1 and 2.64 +/- 1.02 ml min-1 g-1, respectively. MBF values derived from ammonia PET at rest and during hyperaemia were 0.95 +/- 0.23 ml min-1 g-1 and 2.44 +/- 0.81 ml min-1 g-1, respectively. The correlation between the two methods was close (y = 0.92x + 0.14, r = 0.96; P < 0.0001). No indication was found for limited extraction of ammonia in the myocardium. The high concordance of global MBF values derived with argon and ammonia indicates that the implicit correction of spillover and recovery effects, incorporated in the model by including an effective blood volume parameter, works correctly quantitatively. Our data provide the previously missing human validation of MBF measurements from 13N-ammonia PET.

Adenosine↗

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation.

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.

Adolescent↗

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.

Carcinoma, Non-Small-Cell Lung↗