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المؤلفون: Jocelyne Bloch, Jean-François Brunet, Simon Badoud, Véronique Moret, Pauline Chatagny, Cristian Antonescu, Jérôme Cottet, Simon Borgognon, Eric M. Rouiller, Nathalie Ginovart
المصدر: Journal of Alzheimer's Disease and Parkinsonism, Vol. 7, No 5 (2017)
مصطلحات موضوعية: 0301 basic medicine, F-DOPA PET scan, Parkinson's disease, Motor behaviour, Substantia nigra, Cell therapy, 03 medical and health sciences, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, medicine, Autologous transplantation, Progenitor cell, MPTP, Dopaminergic, Macaque monkeys, TH-immunocytochemistry, medicine.disease, Neural stem cell, Transplantation, 030104 developmental biology, chemistry, nervous system, Psychology, Neuroscience, 030217 neurology & neurosurgery
الوصف: Objective: Previous evidence was provided that parkinsonian monkeys exhibited significant though incomplete behavioral recovery following a cell therapy consisting of auto-transplantation of adult neural progenitor cells. The aim of the present study was to assess for the first time in this parkinsonian non-human primate model the striatal dopaminergic function, in parallel to further behavioral assessment. In other words, is the behavioral recovery associated to a reversal of dopaminergic function despite the auto-transplanted cells are not dopaminergic. Methods: Striatal dopaminergic function and motor behavior (spontaneous motion activities) were monitored in adult parkinsonian macaques in relation to autologous neural cell ecosystem (ANCE) transplantation. In four MPTP intoxicated macaques, adult progenitor cells derived from cortical biopsies were re-implanted in the same animal after a phase of spontaneous functional recovery. The function of the striatal dopaminergic system was assessed using 18F-DOPA positron tomography imaging and the motor function was quantified. Results: Two parkinsonian animals exhibited severe motor symptoms, which were moderate and transient in two other monkeys. 18F-DOPA striatal uptake decreased by 80% in three animals, consistent with losses of dopaminergic neurons in substantia nigra and reduced striatal density of dopaminergic projections. Six months after autologous transplantation, all animals improved their motor functions. This functional recovery was largely consistent with positron emission tomography results showing some recovery of 18F-DOPA striatal uptake toward baseline value following transplantation. Conclusion: The present data confirm that symptoms are variable across individual parkinsonian monkeys and that autologous neural cell ecosystem transplantation indeed attenuates parkinsonian motor symptoms. Yet the present study provides for the first time evidence in favor of an increase in the striatal dopaminergic activity that correlates with motor recovery in this novel therapeutic approach, although the implanted cells are not dopaminergic.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::150dd7f95d24765c550e8e000a13a02c
https://archive-ouverte.unige.ch/unige:104855 -
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المؤلفون: Oliver W. Press, John O. Prior, Claudine Helg, Cristian Antonescu, Marek Kosinski, Nicolas Ketterer, Angelika Bischof Delaloye, Franz Buchegger
المصدر: Journal of Nuclear Medicine. 52:896-900
مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, medicine.medical_treatment, 131I-tositumomab, Antineoplastic Agents, Tositumomab, Refractory, Bone Marrow, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Radiometry, Bone Marrow Diseases, Aged, Chemotherapy, business.industry, Lymphoma, Non-Hodgkin, Remission Induction, Antibodies, Monoclonal, Middle Aged, Radioimmunotherapy, Antigens, CD20, Prognosis, medicine.disease, Recombinant Proteins, United States, Lymphoma, Indolent lymphoma, Europe, England, Drug Resistance, Neoplasm, Interferon Type I, Female, Rituximab, Neoplasm Recurrence, Local, Radiopharmaceuticals, business, Switzerland, Follow-Up Studies, medicine.drug
الوصف: UNLABELLED The purpose of our study was to update the safety and efficacy results of radioimmunotherapy in relapsed or resistant indolent or transformed non-Hodgkin lymphoma. METHODS More than 9 y ago, we treated 12 indolent and 4 transformed, relapsed or refractory lymphoma patients with a single administration of nonmyeloablative therapy with tositumomab and (131)I-tositumomab. The 16 patients had a mean of 3.1 (range, 1-6) previous chemotherapy and antibody treatments. RESULTS Six of 12 relapsed indolent lymphoma patients remain disease-free a mean of 9.8 y (range, 8.6-10.7 y) after radioimmunotherapy. Three of 4 transformed lymphoma patients progressed after radioimmunotherapy, and 1 patient had a partial response of 10 mo. CONCLUSION Optimal patient benefit might be obtained in indolent lymphoma when administering radioimmunotherapy up-front in combination with chemotherapy and rituximab treatment. However, these results show that radioimmunotherapy alone achieved long-lasting remissions in 6 of 12 (50%) indolent lymphoma patients in relapse after 1 or multiple chemotherapies.
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المؤلفون: P. Monnin, Carine Grannavel, Marek Kosinski, Francis R. Verdun, Angelika Bischof Delaloye, Nicolas Ketterer, Franz Buchegger, Andreas O. Schaffland, Cristian Antonescu, Tibor Kovacsovics
المصدر: European journal of nuclear medicine and molecular imaging, vol. 32, no. 8, pp. 943-51
مصطلحات موضوعية: Male, Biodistribution, Metabolic Clearance Rate, medicine.medical_treatment, Spleen, Injections, Intralesional, Whole-Body Counting, Drug Administration Schedule, Antibodies, Monoclonal, Murine-Derived, Pharmacokinetics, medicine, Humans, Dosimetry, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Radiometry, Infusions, Intralesional, Antibodies, Monoclonal, Body Burden, Female, Kinetics, Lymphoma, Non-Hodgkin, Middle Aged, Organ Specificity, Radiopharmaceuticals, Radiotherapy Dosage, Relative Biological Effectiveness, business.industry, General Medicine, medicine.disease, Lymphoma, medicine.anatomical_structure, Radioimmunotherapy, Rituximab, Nuclear medicine, business, medicine.drug, Blood sampling
الوصف: PURPOSE: It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated 131I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin's lymphoma (NHL). METHODS: Patients received standard weekly therapy with rituximab (375 mg/m2) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq 131I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post 131I-rituximab injection prior to the second and third injections, respectively. RESULTS: A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T(1/2)beta, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T(1/2) of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48-0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver. CONCLUSION: These results show that the biodistribution and tissue kinetics of 131I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.
وصف الملف: application/pdf
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المؤلفون: Anton Hagenbeek, Angelika Bischof Delaloye, Jens Kuhlmann, Cristian Antonescu, Thomas Louton
المساهمون: Cancer Center Amsterdam, Clinical Haematology
المصدر: Journal of nuclear medicine, 50(11), 1837-1843. Society of Nuclear Medicine Inc.
مصطلحات موضوعية: Adult, Male, Internationality, medicine.medical_treatment, Follicular lymphoma, Radiation Dosage, medicine, Humans, Dosimetry, Radiology, Nuclear Medicine and imaging, Radiometry, Lymphoma, Follicular, Aged, Neoplasm Staging, Chemotherapy, business.industry, Antibodies, Monoclonal, Environmental Exposure, Middle Aged, Radioimmunotherapy, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Absorbed dose, Toxicity, Female, Rituximab, Bone marrow, Nuclear medicine, business, medicine.drug
الوصف: The objective of this analysis was to assess the radiation exposure associated with (90)Y-ibritumomab tiuxetan when used as consolidation therapy in adults with low or minimal tumor burden after first-line therapy of advanced follicular lymphoma (FL). METHODS: The patients who were enrolled in the phase 3 first-line indolent trial were 18 y or older, with CD20(+) grade 1 or 2 stage III or IV FL, and a partial response, complete response, or unconfirmed complete response to first-line chemotherapy. The patients were allocated randomly to receive a single infusion of unlabeled rituximab 250 mg/m(2) on day -7 and consolidation on day 0 with a single dose of (90)Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after unlabeled rituximab, 250 mg/m(2), or no further treatment. On day -7, a subset of patients received an injection of 185 MBq of (111)In-ibritumomab tiuxetan immediately after unlabeled rituximab, 250 mg/m(2), for central dosimetry analysis. Correlations were assessed between organ radiation absorbed dose and toxicity, body weight, body mass index, and progression-free survival. RESULTS: Central dosimetry evaluations were available from 57 of 70 patients. Median radiation absorbed doses were 100 cGy (range, 28-327 cGy) for the red marrow and 72 cGy (range, 46-106 cGy) for the whole body. Radiation absorbed doses did not differ significantly between patients who had a partial response or complete response to initial therapy. Progression-free survival correlated significantly with the whole-body (r = 0.4401; P = 0.0006) and bone marrow (r = 0.2976; P = 0.0246) radiation dose. Body weight was significantly negatively correlated with whole-body radiation dose (r = -0.4971; P < 0.0001). Neither the whole-body radiation dose nor the bone marrow radiation dose correlated with hematologic toxicity. CONCLUSION: In patients with low or minimal residual tumor burden after first-line chemotherapy of advanced FL, whole-body and bone marrow exposure after (90)Y-ibritumomab tiuxetan consolidation showed a significant positive correlation with progression-free survival, whereas dosimetric data could not predict hematologic toxicity
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b46343eed4d034f57ced5ee5070274f5
https://pure.amc.nl/en/publications/dosimetry-of-90yibritumomab-tiuxetan-as-consolidation-of-first-remission-in-advancedstage-follicular-lymphoma-results-from-the-international-phase-3-firstline-indolent-trial(ff0df5f6-ba3c-46f4-939e-8a30540f5e2b).html -
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المؤلفون: Jean-Daniel Tissot, Alain Mantegani, Cristian Antonescu, C. Mayerat, P. C. Frei, François Spertini
المصدر: Blood. 92:3486-3488
مصطلحات موضوعية: musculoskeletal diseases, business.industry, Hepatitis C virus, Immunology, Cell Biology, Hematology, medicine.disease_cause, Biochemistry, Virology, Cryoglobulins, Virus, Titer, Cryoglobulin, Chronic hepatitis, Genotype, Medicine, Rheumatoid factor, business
الوصف: To the Editor: Chronic hepatitis C virus (HCV) infection has only recently been recognized as the leading cause of mixed cryoglobulinemia.[1][1] [2][2] Rheumatoid factor B cells are part of the normal repertoire and significant titers of rheumatoid factors (RF) are induced during normal antiviral
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::e7df9b6c66b245d4632104929a036460
https://doi.org/10.1182/blood.v92.9.3486 -
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المؤلفون: Nicolas Ketterer, Franz Buchegger, Tibor Kovacsovics, Cristian Antonescu, Marek Kosinski, Claudine Helg, A. Bischof Delaloye, Jean-Pierre Mach
المصدر: British journal of cancer, vol. 94, no. 12, pp. 1770-1776
British Journal of Cancerمصطلحات موضوعية: Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, long-term follow-up, Antineoplastic Agents, CHOP, Gastroenterology, Tositumomab, Disease-Free Survival, Time, Internal medicine, Clinical Studies, Medicine, Humans, Progression-free survival, Survival rate, Non-Hodgkin lymphoma, Aged, Chemotherapy, business.industry, Lymphoma, Non-Hodgkin, Antibodies, Monoclonal, Middle Aged, medicine.disease, Survival Analysis, Surgery, Non-Hodgkin's lymphoma, Radiation therapy, Survival Rate, 131I-tositumomab, Treatment Outcome, Oncology, Radioimmunotherapy, radioimmunotherapy, Female, Neoplasm Recurrence, Local, business, medicine.drug
الوصف: We present the long-term results of 18 chemotherapy relapsed indolent (N = 12) or transformed (N = 6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, (131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.
وصف الملف: application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2e8d02b3f444e442928d2b3dd87037b
https://serval.unil.ch/resource/serval:BIB_5BADFEE13999.P001/REF.pdf -
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المؤلفون: Andreas O, Schaffland, Franz, Buchegger, Marek, Kosinski, Cristian, Antonescu, Corinne, Paschoud, Carine, Grannavel, Raimo, Pellikka, Angelika Bischof, Delaloye
المصدر: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 45(10)
مصطلحات موضوعية: Iodine Radioisotopes, Antibodies, Monoclonal, Murine-Derived, Kinetics, Cell Line, Tumor, Isotope Labeling, Antibodies, Monoclonal, Humans, Radioimmunotherapy, Radiopharmaceuticals, Rituximab, Burkitt Lymphoma
الوصف: As part of a search for optimal conditions for radioimmunotherapy of lymphoma, rituximab was labeled with 2 different specific activities of 131I and immunoreactivity was comparatively measured.Labeling was performed with chloramine T using as starting conditions 185 MBq of 131I per 1 mg and per 5 mg of antibody for labelings A and B, respectively. Six comparative labelings were performed over a period of 10 mo with similar efficacy and purified by anion-exchange chromatography. Immunoreactivity was determined immediately after labeling in parallel assays using different concentrations of fresh Raji and Daudi cells. Results were compared at maximal observed specific binding on 10(7) cells and after extrapolation to infinite antigen excess. A statistical analysis was performed to predict the frequency of radiolabeled mono- and polyiodinated antibodies: First, a gaussian distribution predicted the number of iodine atoms per antibody in labelings A and B, respectively; then, the radiolabeling probability was developed according to the Newton binome.Final radiochemical purity was98.4% for all labelings. The final mean specific activities were 169.7 MBq/mg and 32.8 MBq/mg, corresponding to 0.87 and 0.17 iodine atoms per antibody in labelings A and B, respectively. Labeling B showed a significantly higher immunoreactivity than did labeling A, the mean relative increase in binding beingor =28% for both Raji cells and Daudi cells. The predictive statistical analysis indicated that 57.3% and 15.4% of radiolabeled antibodies in labelings A and B, respectively, were polyiodinated.The low specific activity of 131I-rituximab allowed preservation of a high immunoreactivity and correlated with the prediction of a low percentage of polyiodinated radiolabeled antibodies.
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المصدر: Blood. 110:3415-3415
مصطلحات موضوعية: business.industry, Immunology, Ibritumomab tiuxetan, Follicular lymphoma, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, Lymphoma, Medicine, Dosimetry, Rituximab, Peripheral blood cell, business, Nuclear medicine, medicine.drug, Whole blood
الوصف: Yttrium-90 (90Y)-ibritumomab tiuxetan (Zevalin) is an anti-CD20 monoclonal antibody immunoconjugate linked to the pure beta-emitting 90Y radioisotope, which is known to allow targeted delivery limiting normal tissue exposure. As part of the international, phase 3 randomized First-line Indolent Trial (FIT) evaluating the efficacy of Zevalin consolidation compared with observation alone in patients (pts) with advanced stage follicular lymphoma achieving a response to first-line therapy, we investigated the radiation exposure of pts in the Zevalin arm for whom dosimetry data were available. Among the 414 pts enrolled in the trial (age ≥18 yrs, normal peripheral blood cell counts, Median dose in the 57 pts evaluated by central dosimetry was 102 cGy (range 28–327) to RM and 74 cGy (range 46–106) to WB. Radiation exposure was within the protocol-defined upper limits to normal organs (2000 cGy) in all pts and to RM (300 cGy) in all but 2 pts. In one pt, the RM dose was 85175 cGy by local dosimetry, but 94 cGy by central dosimetry; the pt was treated without complications. In the other pt, the RM dose was 327 cGy by central dosimetry, but 155 cGy by local. Average RM exposure was similar between pts with grade 3–4 neutropenia and/or thrombocytopenia and those with grade 0–2. A larger percentage (45%) of the 40 pts with grade 3 or 4 neutropenia had above-average RM radiation dose compared with 18% of the 17 pts with grade 0–2, whereas, the percentage of pts with above-average WB radiation dose was comparable in both groups (42% and 41%, respectively). Overall, neither WB nor RM radiation dose was correlated with hematologic toxicity (Spearman correlation). These findings are consistent with published data (Wiseman et al J Nucl Med2003;44:465–474), and suggest that Zevalin is safely administered in pts with low tumor burden. Our study confirms that radiation exposure with Zevalin treatment is within safe limits to normal organs and that hematologic toxicity does not correlate with RM radiation dose estimates.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::64a5fdd4f6193f0d9d4ef3077f89b078
https://doi.org/10.1182/blood.v110.11.3415.3415 -
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المؤلفون: R. Lemoine, B. Roche, Maurice Matter, Ralph P. Braun, Jean-Pierre Willi, A. Marie Kurt, Danielle Lienard, A. Bischof Delaloye, Joachim Krischer, D. Guggisberg, Donata Rimoldi, Franz Buchegger, Cristian Antonescu, Jean-Philippe Cerottini, Ferdy J. Lejeune
المساهمون: University of Zurich
المصدر: Europe PubMed Central
مصطلحات موضوعية: Oncology, Adult, Male, medicine.medical_specialty, Pathology, Adolescent, Sentinel lymph node, Early Relapse, 610 Medicine & health, Recurrence, Risk Factors, Internal medicine, medicine, Humans, 2741 Radiology, Nuclear Medicine and Imaging, Radiology, Nuclear Medicine and imaging, Clinical significance, Neoplasm Metastasis, Melanoma, Aged, business.industry, Sentinel Lymph Node Biopsy, 10177 Dermatology Clinic, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Lymphatic system, Immunohistochemistry, Female, business, Stage melanoma, Gamma probe
الوصف: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma.Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance.From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p0.0005) were SLN positivity and a high Breslow index.SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.
وصف الملف: schattauer_10_2007_6_244V.pdf - application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72a7cf2b0be96209da5aac60ecba2df0
http://europepmc.org/abstract/med/18084679
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