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Gerhard Glatting

Publications and source records attributed to Gerhard Glatting.

At least 19 recordsLinked to original sources
PubMed2006

Multiple Myeloma: Molecular Imaging with 11C-Methionine PET/CT--Initial Experience.

PURPOSE: To prospectively assess molecular imaging of multiple myeloma (MM) by using the radiolabeled amino acid carbon 11 ((11)C) methionine and positron emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional local ethics committee and the national radiation protection authorities. All patients with MM and control patients gave written informed consent. Nineteen patients with MM (11 women, eight men; age range, 42-64 years) and 10 control patients with hyperparathyroidism without hematologic diseases (six women, four men; age range, 43-75 years) underwent PET/CT 20 minutes after injection of a mean of 1.0 GBq +/- 0.2 (standard deviation) (11)C-methionine. Presence and extent of CT-assessed tumor manifestations and (11)C-methionine bone marrow (BM) uptake were determined on the basis of maximum standardized uptake value (SUV(max)). BM imaging patterns, normal BM, and maximal lesion (11)C-methionine uptake in patients with MM were compared with those in control patients. In two patients with MM, sulfur 35 ((35)S) methionine uptake in freshly isolated BM plasma cells was measured. Values for SUV(max) of groups were compared by using the Mann-Whitney test on a per-patient basis. RESULTS: (35)S-methionine uptake of plasma cells was five- to sixfold higher than in normal BM cells. (11)C-methionine BM uptake in control patients was homogeneous and low. All patients with MM except one with exclusively extramedullary myeloma had (11)C-methionine-positive lesions. Maximal lesion and normal BM (11)C-methionine mean SUV(max) were 10.2 +/- 3.5 and 4.3 +/- 2.0, respectively, and thus were significantly higher than that of BM in the control group (mean, 1.8 +/- 0.3; P < .001). Extramedullary MM was clearly visible in three patients (mean SUV(max), 7.2 +/- 2.4). Additional (11)C-methionine-positive lesions in normal cancellous bone were found in nearly all patients with MM. In pretreated patients with MM, a moderate fraction of osteolytic lesions had no (11)C-methionine uptake. CONCLUSION: On the basis of increased methionine uptake in plasma cells, active MM can be imaged with (11)C-methionine PET/CT.

Adult↗
PubMed2006

Molecular imaging of proliferation in malignant lymphoma.

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) to detect manifestation sites of malignant lymphoma, to assess proliferative activity, and to differentiate aggressive from indolent tumors. In this prospective study, FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma. Sixty minutes after i.v. injection of approximately 330 MBq FLT, emission and transmission scanning was done. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry. FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging. In 11 patients with indolent lymphoma, mean FLT-SUV in biopsied lesions was 2.3 (range, 1.2-4.5). In 21 patients with aggressive lymphoma, a significantly higher FLT uptake was observed (mean FLT-SUV, 5.9; range, 3.2-9.2; P < 0.0001) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma. Linear regression analysis indicated significant correlation of FLT uptake in biopsied lesions and proliferation fraction (r = 0.84; P < 0.0001). In this clinical study, FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading. Due to specific imaging of proliferation, FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation.

Adult↗
PubMed2006

Determination of the immunoreactivity of radiolabeled monoclonal antibodies: a theoretical analysis.

Conjugates of monoclonal antibodies with radioactive nuclides are frequently used in radioimmunotherapy. Because the conjugation procedure may adversely alter the antibody, the immunoreactivity of the antibody must be determined. In this study, we expand the mathematical description of cell-binding assays for the determination of immunoreactivity to include the amount of unlabeled antibody. We describe the relevant equations and constraints and develop a mathematical description of the underlying measurements. The dependence on antibody, on antigen or cell concentration, on the dissociation constant, and on the specific activity is taken into account. The functional dependence of bound labeled antibody on the experimental parameters is given, and the consequences for parameter estimation are discussed. In order to correctly interpret the experimental data for the immunoreactivity, one requires a mathematical model without unnecessary assumptions together with an appropriate nonlinear regression fit.

Antibodies, Monoclonal↗
PubMed2006

Bone marrow transplantation nephropathy after an intensified conditioning regimen with radioimmunotherapy and allogeneic stem cell transplantation.

UNLABELLED: Intensification of the conditioning regimen with a radioactively labeled anti-CD66 antibody is feasible before allogeneic stem cell transplantation. The use of radioimmunotherapy may deliver a significant dose of radiation to the kidneys. We therefore studied the incidence and clinical picture of bone marrow transplantation (BMT) nephropathy in our patients receiving radioimmunotherapy before allogeneic stem cell transplantation. METHODS: This study was a clinical trial of 114 consecutive patients who received conditioning with a radiolabeled anti-CD66 antibody-188Re (n = 93) or 90Y (n = 21)-between 1998 and 2003. RESULTS: Although BMT nephropathy has developed in none of the patients in the [90Y]anti-CD66 group, 6 of 93 patients receiving [188Re]anti-CD66 presented with signs of BMT nephropathy at a median of 11.5 mo after stem cell transplantation. The absorbed renal dose was significantly lower in the 90Y group (4 vs. 7 Gy, P < 0.0001). Of the patients receiving [188Re]anti-CD66 who are alive, BMT nephropathy developed in 19% (6/32). Five of 6 patients with BMT nephropathy received total-body irradiation. The patients presented with elevated serum creatinine, proteinuria, anemia, hypertension, and signs of microangiopathy. All 6 patients in whom BMT nephropathy has developed are alive at a median follow-up of 58 mo after stem cell transplantation, and 1 patient has entered a dialysis program. CONCLUSION: BMT nephropathy appears to be a significant problem after allogeneic stem cell transplantation with intensified conditioning using the 188Re-labeled anti-CD66 applied in this study, particularly when combined with total-body irradiation.

Adolescent↗
PubMed2006

Targeted marrow irradiation with radioactively labeled anti-CD66 monoclonal antibody prior to allogeneic stem cell transplantation for patients with leukemia: results of a phase I-II study.

We treated 20 adult patients with a (188) Re-labeled anti-CD66 antibody (mean marrow dose 13.3 Gy) prior to allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia or advanced chronic myeloid leukemia. The intensified conditioning was not associated with increased non-relapse mortality. No reduction in the incidence of relapse was observed in the context of a T-cell depleted graft (4-year overall survival: 29%).

Adult↗
PubMed2006

Imaging prostate cancer with 11C-choline PET/CT.

UNLABELLED: The ability of 11C-choline and multimodality fusion imaging with integrated PET and contrast-enhanced CT (PET/CT) was investigated to delineate prostate carcinoma (PCa) within the prostate and to differentiate cancer tissue from normal prostate, benign prostate hyperplasia, and focal chronic prostatitis. METHODS: All patients with PCa gave written informed consent. Twenty-six patients with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline PET/CT after intravenous injection of 1,112 +/- 131 MBq 11C-choline, radical retropubic prostatovesiculectomy, and standardized prostate tissue sampling. Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of the prostate were determined. PET/CT results were correlated with histopathologic results, prostate-specific antigen (PSA), Gleason score, and pT stage. RESULTS: The SUV of 11C-choline in PCa tissue was 3.5 +/- 1.3 (mean +/- SD) and significantly higher than that in prostate tissue with benign histopathologic lesions (2.0 +/- 0.6; P < 0.001 benign histopathology vs. cancer). Visual and quantitative analyses of segmental 11C-choline uptake of each patient unambiguously located PCa in 26 of 26 patients and 25 of 26 patients, respectively. A threshold SUV of 2.65 yielded an area under the receiver-operating-characteristic (ROC) curve of 0.89 +/- 0.01 for correctly locating PCa. The maximal 11C-choline SUV did not correlate significantly with PSA or Gleason score but did correlate with T stage (P = 0.01; Spearman r = 0.49). CONCLUSION: 11C-Choline PET/CT can accurately detect and locate major areas with PCa and differentiate segments with PCa from those with benign hyperplasia, chronic prostatitis, or normal prostate tissue. The maximal tumoral 11C-choline uptake is related to pT stage.

Aged↗
PubMed2006

Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.

UNLABELLED: The outcome of hematopoietic cell transplantation for hematologic malignancies may be improved by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the biodistribution of 111In-labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody YAML568 that recognizes a common CD45 epitope present on all human leukocytes. METHODS: Eight patients undergoing bone marrow transplantation received YAML568 labeled with 122 +/- 16 MBq of 111In intravenously followed by serial blood sampling, urine collection, and conjugated view planar gamma-camera imaging up to 144 h after injection. Time-activity curves were obtained using region-of-interest analysis in the accumulating organs and residence times were calculated. An estimate for the radiation-absorbed doses for each organ per unit of administered activity of 90Y was calculated using software for internal dose assessment. The first patient received no unlabeled antibody preloading. The second 2 patients received a preloading dose of 10 mg (0.15 mg/kg). The last 5 patients received a preloading dose of 30-47 mg (0.5 mg/kg). RESULTS: No significant administration-related side effects were seen. The 3 patients receiving no antibody or low antibody preloading had an unfavorable biodistribution with a high initial accumulation of activity in the liver (37%) and the spleen (34%). For the patients receiving 0.5-mg/kg antibody preloading, the estimated radiation-absorbed doses for red bone marrow, spleen, liver, kidney, and total body were 6.4 +/- 1.2, 19 +/- 5, 3.9 +/- 1.4, 1.1 +/- 0.4, and 0.6 +/- 0.1 mGy/MBq, respectively, demonstrating preferential red marrow targeting. A linear regression model showed that the amount of unlabeled antibody preloading per body weight has a strong influence on the estimated red marrow absorbed dose (P = 0.003, R2 = 0.80). CONCLUSION: This study shows that the anti-CD45 monoclonal antibody YAML568 is suitable for delivering selectively radiation to hematopoietic tissues when labeled with 90Y provided that a preloading dose of about 0.5 mg/kg unlabeled antibody is given.

Adult↗
PubMed2005

188Re or 90Y-labelled anti-CD66 antibody as part of a dose-reduced conditioning regimen for patients with acute leukaemia or myelodysplastic syndrome over the age of 55: results of a phase I-II study.

In a phase I-II study for patients aged 55-65 years, we employed radioimmunotherapy using an anti-CD-66 antibody as part of a dose-reduced conditioning regimen, which was followed by a T-cell-depleted graft. 20 patients with a median age of 63 years suffering from acute leukaemia (n=17) or myelodysplastic syndrome (n=3) received the antibody labelled either with 188Rhenium (n=8) or with 90Yttrium (n=12) during conditioning. Radioimmunotherapy provided a mean dose of 21.9 (+/-8.4) Gy to the bone marrow with a significantly higher dose when 90Yttrium was used. Additional conditioning was fludarabine-based plus anti-thymocyte globulin in matched related donor transplants (n=11), or plus melphalan in matched unrelated donor transplants (n=9). Regimen-related toxicity was low, with two patients developing three episodes of grade III organ toxicity. All patients engrafted, grade II-IV acute graft-versus-host disease (GvHD) was observed in one patient (5%) and chronic GvHD in three patients (15%). The cumulative incidence of non-relapse mortality was 25%, the cumulative incidence of relapse 55%. The probability of survival was estimated to be 70% at 1 year and 52% at 2 years post-transplant, although no plateau was reached afterwards. In conclusion, radioimmunotherapy using the anti-CD66 antibody was feasible and safe in our elderly patient group and provided a high marrow dose.

Aged↗
PubMed2005

Internal radionuclide therapy: the ULMDOS software for treatment planning.

Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows one to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.

Algorithms↗
PubMed2005

Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations.

UNLABELLED: We investigated radiation exposure of patients undergoing whole-body 18F-FDG PET/CT examinations at 4 hospitals equipped with different tomographs. METHODS: Patient doses were estimated by using established dose coefficients for 18F-FDG and from thermoluminescent measurements performed on an anthropomorphic whole-body phantom. RESULTS: The most relevant difference between the protocols examined was the incorporation of CT as part of the combined PET/CT examination: Separate low-dose CT scans were acquired at 2 hospitals for attenuation correction of emission data in addition to a contrast-enhanced CT scan for diagnostic evaluation, whereas, at the other sites, contrast-enhanced CT scans were used for both purposes. Nevertheless, the effective dose per PET/CT examination was similar, about 25 mSv. CONCLUSION: The dosimetric concepts presented in this study provide a valuable tool for the optimization of whole-body 18F-FDG PET/CT protocols. Further reduction of patient exposure can be achieved by modifications to the existing hardware and software of PET/CT systems.

Body Burden↗
PubMed2004

Clinical relevance of imaging proliferative activity in lung nodules.

PURPOSE: Recently, the thymidine analogue 3'-deoxy-3'[18F]fluorothymidine (FLT) has been introduced for imaging proliferation with positron emission tomography (PET). In this prospective study, we examined the accuracy of FLT for differentiation of benign from malignant lung lesions and for tumour staging. METHODS: A total of 47 patients with newly diagnosed pulmonary nodules on chest CT suspicious for malignancy were examined with FLT-PET in addition to routine staging procedures. A total of 43 patients also underwent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET imaging. Within 2 weeks, patients underwent resective surgery or core biopsy of the pulmonary lesion. RESULTS: Histopathology revealed malignant lung tumours in 32 patients (20 non-small cell lung cancer, 1 small cell lung cancer, 1 pulmonary carcinoid, 1 non-Hodgkin's lymphoma, nine metastases from extrapulmonary tumours) and benign lesions in 15 patients. Increased FLT uptake was exclusively related to malignant tumours. FLT-PET was false negative in two patients with non-small cell lung cancer, in the patient with a pulmonary carcinoid and in three patients with lung metastases. The sensitivity of FLT-PET for detection of lung cancer was 90%, the specificity 100% and the accuracy 94%. Fifteen out of 21 patients with lung cancer had mediastinal lymph node metastases. FLT-PET was true positive in 7/15 patients, resulting in a sensitivity of 53% for N-staging (specificity 100%, accuracy 67%). Clinical TNM stage was correctly identified in 67% (20/30) patients, compared to 85% (23/27) with FDG-PET. CONCLUSION: FLT-PET has a high specificity for the detection of malignant lung tumours. Compared with FDG, FLT-PET is less accurate for N-staging in patients with lung cancer and for detection of lung metastases. FLT-PET therefore cannot be recommended for staging of lung cancer.

Adult↗
PubMed2004

Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer.

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19-39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14-22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.

Adult↗
PubMed2004

Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.

Aged↗
PubMed2004

Quantitative imaging of yttrium-86 PET with the ECAT EXACT HR+ in 2D mode.

The radionuclide 86Y potentially allows for the precise assessment of tissue radioactivity biodistribution and, thus, extrapolation of a therapeutic dose of 90Y-labeled compounds. A method to obtain quantitative images from 86Y-PET measurements after a background correction and a recalibration is presented. Cylinder and body phantom measurements with 18 F and 86Y using an ECAT EXACT HR+ tomograph were performed in 2D mode. A second-order series expansion is used to correct for the background of spurious coincidences in the sinogram. A recalibration of the positron emission tomography (PET) system, depending on the ratio of true coincidences and singles, is implemented. The correction for the nonannihilation coincidences with a second-order series expansion significantly improves the accuracy of quantitation: The lesion-to-background ratio is reproduced, and the variation of the activity concentration in the homogeneous background regions of the phantoms is smaller than 5%. The apparent activities in cold inserts of various densities is reduced to less than 15% of the concentration in the active region. The recalibration of the system works with a relative error of 0.2% +/- 2.4%. In conclusion, the used approximations lead to improved uniformity and quantitative accuracy in 86Y-PET measurements with the ECAT EXACT HR+.

Calibration↗
PubMed2004

Improving binding potential analysis in [11C]raclopride PET studies using cluster analysis.

To calculate binding potentials (BP) in [11C]raclopride brain PET studies a reference tissue model is widely used. The aim of the present study was to improve the determination of time activity curves (TAC) of reference tissue regions using cluster analysis. In four patients with Huntington disease TACs of a cerebellar reference region were calculated either from manually placed circular ROIs within the cerebellum or by cluster analysis. BP estimates derived from cluster analysis are independent from inter- and intraobserver variations and show an improved reproducibility combined with a low variability compared to manually placed cerebellar ROIs. This is of high value in longitudinal studies.

Adult↗
PubMed2003

A comparison of the biodistribution and biokinetics of (99m)Tc-anti-CD66 mAb BW 250/183 and (99m)Tc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy.

Radioimmunotherapy (RIT) with radiolabelled monoclonal antibodies (mAbs) is an effective method of achieving myeloablation in leukaemia patients prior to stem cell transplantation (SCT). We wished to compare the approaches of specific binding to leukaemic blasts and non-specific binding to benign red marrow cells, which results in a myeloablative "cross-fire" effect. Therefore, we prospectively evaluated the biodistribution and biokinetics of the anti-CD45 mAb YTH 24.5 and the anti-CD66 mAb BW 250/183 with regard to their suitability for myeloablative RIT. The red marrow selective anti-CD66 mAb BW 250/183 (IgG1) binds to normal granulopoietic cells. In contrast, the anti-CD45 mAb YTH 24.5 (IgG2b) binds to 85-90% of acute leukaemic blasts and almost all haematopoietic white cells. Patients with leukaemic blast infiltration of the marrow <25% and assigned for RIT and SCT were included. Twelve patients (eight male, four female; median age 46+/-7 years) with AML (5), CML (5) or ALL (2) were examined. Both mAbs were labelled with technetium-99m. Within 48 h, 906+/-209 MBq (99m)Tc-anti-CD66 mAb and 760+/-331 MBq (99m)Tc-anti-CD45 mAb were injected consecutively. Scintigraphic and urinary measurements were performed 1, 2, 4 and 24 h after injection. Serum activities were evaluated 2, 5, 10, 15, 30 and 60 min and 2, 4 and 24 h after injection. Compared with the anti-CD45 mAb, the anti-CD66 mAb showed an approximately fourfold higher accumulation in the red marrow, a 2.5-fold lower accumulation in the liver and similar accumulation in the kidneys. The serum activity (% of the injected dose) initially decreased faster for the anti-CD45 mAb but was similar for the two mAbs 24 h after injection: 3.3%+/-1.2% (anti-CD66 mAb) and 2.4%+/-1.1% (anti-CD45 mAb). The cumulated urinary excretion was 17%+/-6.6% (anti-CD66 mAb) and 27.3%+/-7.9% (anti-CD45 mAb) 24 h after application. In these patients with low tumour load, the anti-CD66 mAb BW 250/183 showed more favourable properties in terms of biodistribution and pharmacokinetics. Thus, it appears superior to anti-CD45 mAb YTH 24.5 in selectively increasing the marrow dose and avoiding extramedullary organ toxicity.

Adolescent↗
PubMed2003

Quantitative image reconstruction in PET from emission data only using cluster analysis.

Quantitative image reconstruction in positron emission tomography requires attenuation correction. In case the attenuation correction is not measured separately, under certain conditions this can be determined from the emission data alone. We present a method based on cluster analysis that assumes only 3 empirical attenuation coefficients, i.e., 0.095 cm-1 for soft tissue, 0.02 cm-1 for lung, and 0 cm-1 for air. The subsequent image reconstruction takes place in an iterative fashion, through maximization of image likelihood. For the mathematical thorax phantom used in the present study, the results are comparable to those obtained after separate measurement of the attenuation correction.

Cluster Analysis↗