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Sven N Reske

Publications and source records attributed to Sven N Reske.

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

Intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter in restenotic lesions of native coronary arteries and venous bypass grafts.

PURPOSE: We have previously demonstrated the efficacy of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in a randomised trial including de novo lesions. Percutaneous coronary interventions in restenotic lesions and in stenoses of venous bypass grafts are characterised by a high recurrence rate for restenosis and re-interventions. Against this background, we wanted to assess the impact of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in restenotic lesions in native coronary arteries and venous bypass grafts. METHODS: In 243 patients, beta-brachytherapy with 22.5 Gy was applied at a tissue depth of 0.5 mm. Patients were followed up angiographically after 6 months and clinically for 12 months. The primary clinical endpoint was the incidence of MACE (death, myocardial infarction, target vessel revascularisation). Secondary angiographic endpoints were late loss and binary restenosis rate in the total segment. RESULTS: All irradiation procedures were successfully performed. A total of 222 lesions were in native coronary arteries; 21 were bypass lesions. Mean irradiation length was 41.6+/-17.3 mm (range 20-150 mm) in native coronary arteries and 48.1+/-33.9 mm (range 30-180 mm) in bypass lesions; the reference diameter was 2.57+/-0.52 mm and 2.83+/-0.76 mm, respectively. There was no vessel thrombosis during antiplatelet therapy. Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the native coronary artery group and 38.1% in the CABG group (p<0.03). Binary restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38+/-0.72 mm and 1.33+/-1.11 mm (p<0.001), respectively. CONCLUSIONS: We conclude that intracoronary beta-brachytherapy with a liquid (188)Re-filled balloon using 22.5 Gy at a tissue depth of 0.5 mm in restenotic lesions is safe. It is associated with a low binary restenosis rate, resulting in a low occurrence rate of MACE within 12 months in restenotic lesions in native coronary arteries but not in vein grafts.

Adult↗
PubMed2006

Synthesis and evaluation of a radiometal-labeled macrocyclic chelator-derivatised thymidine analog.

Several radiolabeled thymidine analogs as metabolic probes of cell proliferation were developed specifically addressing DNA synthesis. Thymidine analogs containing carboranylalkyl groups for neutron capture therapy at the N-3 position were found to be good substrates for cytosolic thymidine kinase 1 (TK1). According to this approach, a DO3A macrocycle in N-3 position was attached to thymidine. The 3-DO3A thymidine analog was labeled with 68Ga and 111In. Different lipophilicities of the corresponding radiometal-thymidines were detected via RP-HPLC. [111In]DO3A-thymidine ([111In]D3T) was evaluated for cellular uptake in different cell lines (HL60 and DoHH2). Cellular uptake was low in both cell lines. Phosphorylation of the radioconjugates by TK1 was negligible. Although stable complexation of radiometals to thymidine was obtained, introduction of the macrocycle DO3A reduced the affinity to cytosolic TK1 drastically. Low cellular uptake can be ascribed to missing substrate specificity of [111In]DO3A-thymidine for TK1. The absence of substrate specificity may be due to the bulky macrocyclic chelator and partial charges remaining on the coordination sphere due to a more complex solution structure.

Chelating Agents↗
PubMed2006

Is 3'-deoxy-3'-(18)F-fluorothymidine a better marker for tumour response than (18)F-fluorodeoxyglucose?

3'-Deoxy-3'-(18)F-fluorothymidine (FLT) was developed in 1998 by Shields and co-workers because monitoring of treatment response would be facilitated by imaging agents able to provide measures of tissue and tumour proliferation. Since then, FLT metabolism has been clarified in more detail in cell culture and experimental animal tumour models and also in clinical studies. Recently, FLT has increasingly been used for the assessment of response to anticancer treatment, mainly in tumour xenograft SCID mouse models; in contrast, clinical data are scarce. In this article we briefly summarise the intermediary metabolism of FLT and its application as an anticancer treatment response probe. The potential value and limitations of FLT as a highly promising proliferation imaging probe and its use for monitoring of treatment response are discussed.

Animals↗
PubMed2006

Functional imaging of neuroendocrine tumours with PET.

Several pathophysiological attributes of neuroendocrine tumours (NET) can be addressed by specific radiolabelled probes. This paper provides an overview on the different radiopharmaceuticals that have been developed for Positron Emission Tomography (PET) of neuroendocrine tumours. A review of the literature on 18F-fluordeoxyglucose (FDG), biogenic amine precursors, somatostatin analogues and hormone syntheses markers is presented. Due to the highly specific tracers that lack any clear anatomical landmarking the advantages of integrated PET/CT are obvious. Amine precursors should be employed in most gastroenteropancreatic NET, FDG should be preserved for more aggressive, less differentiated NETs. Somatostatin analogues are the most promising tracers, since they can improve dosimetry in cases in which radiopeptide therapies are planned. In conclusion, the individual diagnostic approach using PET or the integrated PET/CT should be tailored depending on the histological classification and the differentiation of the tumour.

Animals↗
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

Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography.

PURPOSE: To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS: By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION: Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

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↗
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

Biological characterisation of breast cancer by means of PET.

Breast cancer is associated with increased glucose consumption and can therefore be visualised with the glucose analogue [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) and positron emission tomography (PET). FDG uptake in the primary tumour can vary substantially, and specific tumour characteristics have been demonstrated to determine the degree of glucose metabolism. Factors with a major influence on FDG uptake in breast cancer comprise expression of glucose transporter Glut-1 and hexokinase I, number of viable tumour cells per volume, histological subtype, tumour grading, microvessel density and proliferative activity. Recently, an association between high FDG uptake and a worse prognosis was suggested. Several studies have been performed correlating FDG uptake with a variety of prognostic and molecular biomarkers as well as parameters predicting tumour response to therapy. However, a correlation with important clinical prognostic markers such as axillary lymph node status and size of the primary tumour, expression of oestrogen and progesterone receptors, proto-oncogene c-erbB-2 or VEGF could not be demonstrated. The lack of correlation with important markers of prognosis does not suggest that FDG uptake might be used as a prognostic criterion in breast cancer. Innovative radiotracers for specific imaging of tumoural perfusion ([(15)O]H(2)O), hormone receptor expression ([(18)F]FES), protein synthesis ([(11)C]methionine), proliferation rate ([(18)F]FLT) or bone mineralisation ([(18)F]fluoride) may provide additional information compared with that provided by FDG PET.

Biomarkers, Tumor↗
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↗