| 1. |
- Bansch, Peter, et al.
(author)
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Effect of charge on microvascular permeability in early experimental sepsis in the rat.
- 2011
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In: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 82, s. 339-345
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Journal article (peer-reviewed)abstract
- A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for (125)I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for (131)I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3h after sepsis was induced by cecal ligation and incision (CLI) (n=11) and in control animals (n=12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38±3ml/kg and 47±4mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7±4.1% in the controls to 20.1±1.9% following CLI. Corresponding values for cBSA were 26.7±5.6% and 29.8±3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62±0.1 in the control group and 1.49±0.1 following CLI (p<0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.
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| 2. |
- Bjurberg, Maria, et al.
(author)
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Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.
- 2009
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In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:3, s. 327-332
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Journal article (peer-reviewed)abstract
- AIM: The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS: In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS: An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS: Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.
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| 3. |
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| 4. |
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| 5. |
- Bjurberg, Maria, et al.
(author)
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Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer
- 2009
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In: International Journal of Gynecological Cancer. - Philadelphia : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 19:9, s. 1600-1605
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Journal article (peer-reviewed)abstract
- Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.
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| 6. |
- Brun, Eva, et al.
(author)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
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Journal article (peer-reviewed)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 7. |
- Brun, Eva, et al.
(author)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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In: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 8. |
- Elgström, Erika, et al.
(author)
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Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.
- 2014
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In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:4, s. 143-152
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Journal article (peer-reviewed)abstract
- Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.
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| 9. |
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| 10. |
- Elgström, Erika, et al.
(author)
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Pattern of antigen expression in metastases after radioimmunotherapy of a syngeneic rat colon carcinoma utilizing the BR96 antibody.
- 2012
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In: Experimental hematology & oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 1:1
-
Journal article (peer-reviewed)abstract
- Abstract ABSTRACT: BACKGROUND: Repeated administration of antibody-based therapies such as radioimmunotherapy depends on preserved antigen expression in tumor lesions. The purpose of this study was to evaluate whether the antigen expression in metastases observed after radioimmunotherapy differs from that of untreated primary tumors. FINDINGS: 30 of the 35 Brown Norway rats with syngeneic colon carcinoma treated with 400 MBq/kg 177Lu-DOTA-BR96 exhibited consistent complete response of the primary tumor. 13 animals developed metastases that were detected after treatment. The antigen expression was reduced in 17 of 23 metastases detected after radioimmunotherapy compared with untreated tumors. No tumors completely lacked positively stained tumor cells. CONCLUSIONS: Although it was not possible to demonstrate that the antigen reduction is triggered by the radioimmunotherapy this result stress the importance of considering the risk of reduced antigen expression in metastases after radioimmunotherapy prior to further targeted therapies.
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| 11. |
- Elgström, Erika, et al.
(author)
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Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.
- 2015
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 5
-
Journal article (peer-reviewed)abstract
- CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.
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| 12. |
- Engvall, Christian, et al.
(author)
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Human cerebral blood volume (CBV) measured by dynamic susceptibility contrast MRI and 99mTc-RBC SPECT.
- 2008
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In: Journal of Neurosurgical Anesthesiology. - 1537-1921. ; 20:1, s. 41-44
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with elevated intracranial pressure risk compromising their cerebral blood flow, resulting in ischemia. Lowering of the raised intracranial pressure, is therefore, mandatory. Reduction of the cerebral blood volume (CBV) might be target. In finding ways to do so, one has to be able to measure CBV. Measurement of CBV is, however, difficult. Radio(99mTc-)labeled erythrocytes (99mTcRBC) single photon emission computer-aided tomography (SPECT) is one established method used for CBV measurement. Recently, dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), has also been successfully used for this purpose. The aim of this study was to validate the use of DSC-MRI for the measurement of CBV by the investigation of the correlation between the regional distributions of 99mTc-RBC SPECT and DSC-MRI measurement of CBV in humans. If possible, the aim was also to find a conversion constant that will enable the DCS-MRI to be interpreted as CBV (percent of brain volume). METHODS: CBV of 8 volunteers were studied under normocapnic and hypocapnic conditions. CBV was measured with both 99mTc-RBC SPECT and DSC-MRI. RESULTS: There were significant correlations between the regional distributions of CBV measured by 99mTc-RBC SPECT and DSC-MRI (rest: F=4.53, P<0.05; hypocapnia: F=9.61, P<0.005). The derived conversion factor between DSC-MRI voxel values and 99mTc-RBC SPECT CBV (percent of brain volume) at rest was 0.0059+/-0.0013. Global CBV during normocapnia was 4.3%+/-0.6% of brain volume as measured by SPECT of brain volume and 4.5%+/-0.9% as measured by MRI. Decreasing the end-tidal pCO2 by 1.8 kPa by spontaneous hyperventilation reduced the global CBV significantly to 3.9%+/-0.5% in the SPECT group and to 3.5%+/-0.6% in the MRI group. CONCLUSIONS: The comparison of 99mTc-RBC SPECT and DSC-MRI measurements in our study indicates that DSC-MRI can be a useful method to measure CBV as a percent of brain volume.
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| 13. |
- Eriksson, Sophie, et al.
(author)
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Repeated Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
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In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:2, s. 134-140
-
Journal article (peer-reviewed)abstract
- Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose. Results: The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases. Conclusions: In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity.
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| 14. |
- Eriksson, Sophie, et al.
(author)
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Sequential Radioimmunotherapy with (177)Lu- and (211)At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2014
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In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:6, s. 238-246
-
Journal article (peer-reviewed)abstract
- Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.
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| 15. |
- Eriksson, Sophie, et al.
(author)
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Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.
- 2012
-
In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 27:3, s. 175-182
-
Journal article (peer-reviewed)abstract
- Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.
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| 16. |
- Garkavij, Michael, et al.
(author)
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Lu-177-[DOTA0,Tyr3] Octreotate Therapy in Patients With Disseminated Neuroendocrine Tumors: Analysis of Dosimetry With Impact on Future Therapeutic Strategy
- 2010
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In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1084-1092
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Journal article (peer-reviewed)abstract
- BACKGROUND: Lu-177-(DOTAO,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. METHODS: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. RESULTS: For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084-92. (C) 2010 American Cancer Society.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Henriksson, Eva, et al.
(author)
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2-deoxy-2-[F-18]fluoro-D-glucose uptake and correlation to intratumoral heterogeneity
- 2007
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In: Anticancer research. - 1791-7530. ; 27:4B, s. 2155-2159
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in relation to the intratumoral histopathological appearance. Materials and Methods: Intratumoral distribution of FDG in nude mice with xenografted tumours originating from an established head and neck squamous cell carcinoma was studied. FDG uptake and the con-elation to histopathological appearance was evaluated in four separate quarters of each tumour. Results: Variations in FDG uptake correlating to the presence of tumour cells was demonstrated. Quarters containing more than 50% tumour cells showed a significantly higher FDG uptake (p=0.028) than quarters with more stromal tissue and necrosis. Conclusion: This Study shows that the heterogenic FDG uptake within a tumour correlates to histopathological findings and that the variable appearance of tracer uptake on the PET scan depends on distribution of different tissue components in the tumour. This intratumoral heterogeneity calls for caution when evaluating a PET scan where median values of larger areas will be misguiding and thus small areas with high uptake should be regarded as the regions of interest.
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| 21. |
- Henriksson, Eva, et al.
(author)
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Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck
- 2009
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In: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 28
-
Journal article (peer-reviewed)abstract
- Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test ( crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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| 22. |
- Josefsson, Malin, et al.
(author)
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Sodium/iodide-symporter: distribution in different mammals and role in entero-thyroid circulation of iodide.
- 2002
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In: Acta Physiologica Scandinavica. - 0001-6772. ; 175:2, s. 129-137
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Journal article (peer-reviewed)abstract
- The sodium (Na+)/iodide (I-)-symporter (NIS) is abundantly expressed and accumulates iodide in thyroid follicular cells. The NIS is also found in extrathyroidal tissues, particularly gastric mucosa. Controversies exist on the localization of extrathyroidal NIS. We have studied the presence of both NIS peptide and NIS messenger RNA (mRNA) in the digestive tract and thyroid from different mammals. The role of gastric NIS is enigmatic and we aimed to unravel its possible involvement in iodide transport. Methods: Distribution and expression of NIS were studied using immunocytochemistry and in situ hybridization. Iodide transport in the gastrointestinal tract was measured after oral or intravenous (i.v.) administration of 125I to rats with or without ligation of the pylorus. Results: All thyroid follicular cells in rat and mouse expressed NIS, whereas a patchy staining was noted in man, pig and guinea-pig. Gastric mucosa surface epithelium in all species and ductal cells of parotid gland in guinea-pig, rat and mouse expressed NIS. In parietal cells and in endocrine cells of intestines and pancreas NIS immunoreactivity but no NIS mRNA was found. Studies of 125I uptake showed marked iodide transport from the circulation into the gastric lumen. Conclusions: The localization of NIS varies slightly among mammals. To establish expression of NIS in a particular cell type the need to correlate the presence of both NIS protein by immunocytochemistry and NIS mRNA by in situ hybridization is emphasized. An entero-thyroidal circulation of iodide mediated principally by gastric NIS, but possibly also by NIS in salivary glands is suggested.
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| 23. |
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| 24. |
- Kjölhede, Henrik, et al.
(author)
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Combined (18) F-fluorocholine and (18) F-fluoride positron emission tomography/computed tomography imaging for staging of high-risk prostate cancer.
- 2012
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In: BJU International. - 1464-4096. ; 110:10, s. 1501-1506
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Journal article (peer-reviewed)abstract
- Study Type - Diagnosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Positron emission tomography/computed tomography (PET/CT) with choline and fluoride for the detection of metastases in patients with prostate cancer have each been evaluated, with mixed results. Choline PET/CT has been evaluated against pelvic lymphadenectomy, generally with a low sensitivity but a high specificity; however, the study populations have been heterogenous. Fluoride PET/CT has been evaluated against other imaging methods, such as bone scan, single photon emission CT and MRI, and has been shown to have high specificity as well as sensitivity for bone metastases, but there are no studies with biopsy verification. This is the first study that evaluates the clinical use of both choline and fluoride PET/CT on the same patients in a well-defined population of patients with high-risk prostate cancer. OBJECTIVE: • To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both (18) F-fluorocholine and (18) F-fluoride as markers, add clinically relevant information for patients with prostate cancer who have high-risk tumours and a normal or inconclusive planar bone scan. PATIENTS AND METHODS: • Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8-10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a (18) F-fluorocholine and a (18) F-fluoride PET/CT. • None of the patients received hormonal therapy before the staging procedures were completed. RESULTS: • For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases. • (18) F-fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%). • (18) F-fluoride PET/CT was suggestive for bone metastases in 37 patients (41%). • In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non-curative. • Of the patients with positive scans, 74% had Gleason score 8-10 tumours. Of the patients with Gleason score 8-10 tumours, 64% had positive scans. CONCLUSIONS: • PET/CT scans with (18) F-fluorocholine and (18) F-fluoride commonly detect metastases in patients with high-risk prostate cancer and a negative or inconclusive bone scan. • For 20% of the patients the results of the PET/CT scans changed the treatment plan.
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| 25. |
- Lindén, Ola, et al.
(author)
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131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing chemotherapy. Treatment outcome, haematological toxicity and bone marrow absorbed dose estimates.
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 297-303
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Journal article (peer-reviewed)abstract
- The experience with radioimmunotherapy in B-cell lymphomas using the rapidly internalizing antibody, anti-CD22 (LL2), is limited. In this study we investigated the efficacy and toxicity of 131I-labelled-LL2 for radioimmunotherapy in patients with B-cell lymphomas that failed one or two cytostatic regimens. Eleven patients were treated with one or repeated cycles of 131I-anti-CD22 antibody, 1330 MBq/m2 (36 mCi/m2). Six of the 11 treated patients demonstrated an objective response, three of them with complete remission. All follicular (3 patients) and transformed lymphomas (2 patients) responded compared to one of four diffuse large B-cell lymphomas. Two out of six responders exhibited event-free survival (EFS), which was comparable with or longer than the EFS following primary anthracycline-containing chemotherapy. Non-haematological toxicity was mild. Haematological toxicity was associated with pretreatment clinical characteristics but not with estimated absorbed bone marrow doses. Objective remission following treatment with 131I-anti-CD22 can be achieved in patients with various subtypes of B-cell lymphomas, failing standard chemotherapy. Follicular or transformed lymphomas seem particularly responsive. Haematological toxicity seems to be dependent on the functional status of the bone marrow before radioimmunotherapy.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Lindén, Ola, et al.
(author)
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Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas
- 1999
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In: Clinical Cancer Research. - 1078-0432. ; 5:10 Suppl, s. 3287-3291
-
Journal article (peer-reviewed)abstract
- Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.
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| 30. |
- Mårtensson, Linda, et al.
(author)
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Determining maximal tolerable dose of the monoclonal antibody BR96 labeled with 90Y or 177Lu in rats: establishment of a syngeneic tumor model to evaluate means to improve radioimmunotherapy.
- 2005
-
In: Clinical Cancer Research. - 1078-0432. ; 11:19 Pt 2, s. 7104-7108
-
Journal article (peer-reviewed)abstract
- Purpose: To evaluate therapeutic strategies, it is essential to use biological models reflecting important aspects of the clinical situation. The aim of the present study was to compare the maximal tolerable dose of the monoclonal antibody BR96 labeled with Y-90 or Lu-177 in immunocompetent rats. Maximal tolerable dose was defined as the highest activity that allows 100% of the animals to survive without clinical signs, such as infections, bleeding, or diarrhea, and with < 20% loss in body weight. Experimental Design: Increasing activity levels of BR96 labeled with Y-90 or Lu-177 were administered to groups of rats. Blood parameters, body weight, and general performance were monitored for 8 weeks. Results: Two days postinjection, all groups had decreased leukocyte counts down to 5% to 15% of initial values. Initiation of recovery (at 14-21 days) showed a dose-response relationship. All groups, except the group given the highest activity of Y-90 had complete resolution in their leukopenia. The decrease in platelets was delayed to days 7 to 14 postinjection with a dose dependent response regarding both severity of the nadir (10-40% of initial value) and the start of recovery. Animals in the groups given the highest activities of both Y-90 and Lu-177 exhibited skin infections on day 21. Conclusions: The results showed good reproducibility and dose-dependent toxicity for both radionuclides, indicating that the maximal tolerable dose for Lu-177 - BR96 (1,000 MBq/kg) is 1.7 times that for Y-90 - BR96 (600 MBq/kg) in rats. This model makes it feasible to evaluate strategies to escalate therapeutic doses to tumors without increasing normal tissue toxicity.
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| 31. |
- Mårtensson, Linda, et al.
(author)
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High-Dose Radioimmunotherapy Combined With Extracorporeal Depletion in a Syngeneic Rat Tumor Model
- 2010
-
In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1043-1052
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors in an immunocompetent animal model. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed by analysis of blood parameters for 12 weeks. The effect of increased doses in combination with extracorporeal affinity adsorption treatment was evaluated with respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer model. RESULTS: The MTD of Lu-177- or Y-90-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with Lu-177- or Y-90-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: Extracorporeal affinity adsorption treatment is a method that safely and efficiently reduces myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. However, because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity in combination with extracorporeal affinity adsorption treatment in this study. Targeted RIT with beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. (C) 2010 American Cancer Society.
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| 32. |
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| 33. |
- Mårtensson, Linda, et al.
(author)
-
Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy
- 2007
-
In: Clinical Cancer Research. - 1078-0432. ; 13:18, s. 5572-5576
-
Journal article (peer-reviewed)abstract
- Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated antibody by ECAT before injection of DOTA-streptavidin increased the tumor targeting by 50%. In addition, the levels of DOTA-streptavidin in liver and lymph nodes were reduced by 60%, which implied a 4.3- and 3.8-fold increase of tumor-to-liver and tumor-to-lymph node ratios, respectively. By doing a second ECAT to remove DOTA-streptavidin from the circulation, accumulation in normal tissues was reduced. However, this latter ECAT also reduced tumor accumulation by 25% (mostly corresponding to radioactivity in the circulation). Conclusions: ECAT was efficient as a means of removing biotinylated antibodies and would probably also be efficient for the clearance of streptavidin-conjugated antibodies. Conversely, the use of ECAT for removal of radiolabeled streptavidin seems not to offer any advantage.
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| 34. |
- Mårtensson, Linda, et al.
(author)
-
Reduced myelotoxicity with sustained tumor concentration of radioimmunoconjugates in rats after extracorporeal depletion.
- 2007
-
In: Journal of Nuclear Medicine. - 0161-5505. ; 48:2, s. 269-276
-
Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the possibility of decreasing the myelotoxicity associated with radioimmunotherapy (RIT) by extracorporeal depletion of radioimmunoconjugates (RIC) from the circulation. The optimal combination of radionuclide and the time interval between injection of the RIC and the subsequent extracorporeal depletion procedure was assessed in immunocompetent rats, with respect to both myelotoxicity and tumor concentration of RIC. Methods: Rats were injected with (177)tumor Y-90-labeled antibody conjugate (mAb-DOTA-biotin) (mAb is monoclonal antibody; DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment (ECAT) 12, 24, or 48 h after injection. Myelotoxicity was assessed by analysis of blood parameters for 10 wk. The effect of ECAT on the tumor concentration of RIC was evaluated in parallel by scintillation camera imaging in rats injected with In-111-labeled RIC. Results: ECAT reduced the blood content of RIC by 95%. Thus, myelotoxicity was significantly milder in animals subjected to ECAT than that in controls. The timing of ECAT influenced the rate and level of bone marrow recovery, with an earlier recovery in animals subjected to ECAT early after injection. The toxicity-reducing effect of ECAT was more distinct in animals injected with Lu-177-labeled RIC than in animals injected with 90Y-labeled RIC. Scintillation camera imaging of tumors before and after ECAT revealed that subjecting animals to ECAT at 12 h after injection considerably reduced the total activity in tumors (34%), whereas the effect was lower at both 24 h (18%) and 48 h (18%) after injection. Conclusion: ECAT can efficiently reduce myelotoxicity associated with RIT, and the concentration of RIC in tumor can be sustained, provided ECAT is performed at an optimal time after antibody administration. The choice of radionuclide for RIT in combination with ECAT is important, as the physical half-life is crucial for the toxicity-reducing potential of ECAT at a specific time.
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| 35. |
- Ohlsson, Tomas G
(author)
-
A clinical positron emission tomography facility : 2-¹⁸FDG studies : development and results
- 1996
-
Doctoral thesis (other academic/artistic)abstract
- Positron emission tomography (PET) is a tracer technique used for quantitative in vivo studies of physiological and biochemical processes. Because of the use of positron-emitting radionuclides such as 11-C, 13-N, 15-O and 18-F, which are isotopes of the biologically ubiquitous elements, it is possible to label radiopharmaceuticals which trace biochemical processes precisely. In order to be able to utilize these useful positron-emitting radiopharmaceuticals without state-of-the-art PET systems, it is interesting to develop alternatives to standard commercial PET facilities. Two different types of nuclear physics research accelerators have been used for the production of [18-F]fluoride, and the isotope produced has been used for radiolabelling of 2-[18F]fluoro-2-deoxy-D-glucose (2-18FDG). A rotating PET scanner, based on two scintillation camera heads, has been developed and used for human 2-18FDG studies. The suitability of an energy window in the Compton region for imaging 511 keV photons in scintillation camera systems has been evaluated. A new simplified method of normalizing clinical 2-18FDG PET results has been developed and validated, using erythrocytes as a reference tissue, requiring only one blood sample in the middle of the PET scan to calculate the integrated 2-18FDG input function with an accuracy better than ± 8%. An investigation using 2-18FDG PET to monitor the effect of therapy in advanced head and neck cancer patients has been performed. We found that low initial metabolic rate of glucose (MRgl ) predicted a complete local response. The second PET examination gave no further information for this group. In the group of primary tumours and lymph node metastases representing a combination of high initial MRgl and a small decrease in MRgl at the second PET examination, the outcome was unfavourable. An accurate normalization of 2-18FDG uptake was essential to evaluate the results of this study.
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| 36. |
- Olanders, Knut, et al.
(author)
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The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats.
- 2002
-
In: Shock. - 1540-0514. ; 18:1, s. 86-92
-
Journal article (peer-reviewed)abstract
- Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17-45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.
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| 37. |
- Reinstrup, Peter, et al.
(author)
-
Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O)
- 2001
-
In: Anesthesiology. - 1528-1175. ; 95:5, s. 1079-1082
-
Journal article (peer-reviewed)abstract
- BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. METHODS: Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.
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| 38. |
- Reinstrup, Peter, et al.
(author)
-
Regional cerebral metabolic rate (positron emission tomography) during inhalation of nitrous oxide 50% in humans
- 2008
-
In: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 100:1, s. 66-71
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Recent studies in man have shown that cerebral blood flow increases during inhalation of nitrous oxide (N2O), a finding which is believed to be a result of an increased cerebral metabolic rate (CMR). However, this has not previously been evaluated in man. METHODS: Regional CMR(glu) (rCMR(glu)) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. RESULTS: Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)]. Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1) min(-1)] significantly, but it changed the distribution of the metabolism in the brain (P<0.0001 analysis of variance). Compared with inhalation of O2 30% in N2, N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%, P<0.05] and thalamus [22 (23) %, P<0.05]. There was a prolonged metabolic effect of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air (P<0.0001) performed 1 h after the N2O administration. CONCLUSIONS: Inhalation of N2O 50% did not change global CMR(glu), but the metabolism increased in central brain structures, an effect that was still present 1 h after discontinuation of N2O.
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| 39. |
- Siikanen, Jonathan, et al.
(author)
-
A niobium water target for routine production of [(18)F]Fluoride with a MC 17 cyclotron.
- 2013
-
In: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043. ; 72C, s. 133-136
-
Journal article (peer-reviewed)abstract
- A [(18)F]Fluoride water target was constructed for a Scanditronix MC 17 cyclotron, without a beam line, with a typical wide beam of ∼30×5mm(2). Niobium was used as target chamber material. One hour irradiation with 45μA protons yields about 110GBq [(18)F]Fluoride. The saturation yield is 8.0±0.6GBq/μA (EOB). The FDG yield is 60±5% (EOS) with a TracerLab MX (G.E. Healthcare). More than 100GBq FDG is routinely produced after a 2h irradiation.
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| 40. |
- Siikanen, Jonathan, et al.
(author)
-
A Peristaltic Pump Driven Zr-89 Separation Module
- 2012
-
In: 14th International Workshop on Targetry and Target Chemistry. - : AIP. - 1551-7616 .- 0094-243X. ; 1509, s. 206-210
-
Conference paper (peer-reviewed)abstract
- To facilitate the separation of Zr-89 produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced Zr-89 - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated Zr-89 activity was investigated for labeling of the HER2-binding monoclonal antibody fragment, trastuzumab-Fab.
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| 41. |
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| 42. |
- Thorngren-Jerneck, Kristina, et al.
(author)
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Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy
- 2001
-
In: Pediatric Research. - 1530-0447. ; 49:4, s. 495-501
-
Journal article (peer-reviewed)abstract
- Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-(F-18) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 µCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p < 0.01). Six infants with mild HIE had a mean (range) CMRgL of 55.5 (37.7-100.8) mol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) µmol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 µmol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) µmol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) µmol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome.
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| 43. |
- Thorngren-Jerneck, Kristina, et al.
(author)
-
Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs
- 2001
-
In: Journal of Neuroscience Research. - : Wiley. - 1097-4547 .- 0360-4012. ; 66:5, s. 844-850
-
Journal article (peer-reviewed)abstract
- The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.
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| 44. |
- Wang, Zhongmin, et al.
(author)
-
Application of extracorporeal immunoadsorption to reduce circulating blood radioactivity after intraperitoneal administration of indium-111-HMFG1-biotin.
- 2002
-
In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4 Suppl, s. 1287-1292
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Extracorporeal immunoadsorption (ECAT) is a method of reducing activity in radiosensitive organs by removing excess monoclonal antibodies (MAbs) from the blood. Previously, the authors experimentally evaluated ECAT based on the avidin-biotin concept after intravenous administration of radioimmunoconjugates. The aim of the current study was to determine whether ECAT could be used to reduce activity after intraperitoneal (i.p.) administration of indium-111((111)In)-HMFG1-biotin in rats, and to compare the pharmacokinetics of (111)In-HMFG1 with or without attached biotin after i.p. injection. METHODS: HMFG1, a murine immunoglobulin G(1) MAb that recognizes an epitope on the polymorphic epithelial mucin (PEM) antigen, was labeled with (111)In and then biotinylated. ECAT was explored from unseparated blood using an avidin-agarose adsorption column. Thirty rats were used as controls and 13 underwent ECAT. The whole-body (WB), blood, and organ activity were monitored. RESULTS: The binding capacity of (111)In-HMFG1-biotin to avidin was high. Biotinylation did not enhance the excretion of HMFG1. When ECAT was employed, the WB and blood radioactivity were reduced by 35-40% (P < 0.05) and 75--86% (P < 0.01), respectively. After the completion of ECAT, the activity uptake in organs was significantly decreased. CONCLUSIONS: ECAT was successfully applied after i.p. injection of the (111)In-HMFG-biotin MAb to reduce the radioactivity in the WB, blood, and radiosensitive organs. Due to redistribution of the radiolabeled MAbs during and after the completion of ECAT, the adsorption may have been prolonged or repeated. Biotinylation did not significantly change the biodistribution of the (111)In-HMFG1 in rats after intraperitoneal injection.
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| 45. |
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| 46. |
- Wang, Zhongmin, et al.
(author)
-
Blood pharmacokinetics of various monoclonal antibodies labeled with a new trifunctional chelating reagent for simultaneous conjugation with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid and biotin before radiolabeling.
- 2005
-
In: Clinical Cancer Research. - 1078-0432. ; 11:19 Pt 2, s. 7171-7177
-
Journal article (peer-reviewed)abstract
- Purpose: Knowledge of the blood pharmacokinetics of monoclonal antibodies is crucial in deciding the optimal time for starting the administration of a "clearing agent"or using a "clearing device." The primary purpose was to investigate whether the pharmacokinetics of various antibodies labeled with the same chelator and In-111 differed significantly after i.v. injection in immunocompetent rats. A new trifunctional chelator called "1033" containing a biotin and a radiometal chelation moiety is introduced, making it possible to use only one conjugation procedure for the antibody. Experimental Design: Sixty-five non - tumor-bearing rats were included and divided into four groups (I-IV). The blood pharmacokinetics was investigated for rituximab, BR96, and trastuzumab labeled with 1033 and In-111 (I-III). The whole-body activity and activity uptake in muscle, liver, and kidney, which might explain differences in the early pharmacokinetics in blood, were also measured. hMN14 labeled with another chelator [1,4,7,10 -tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)], but with the same radionuclide ((111) In-biotin-DOTA-hMN14), was studied (IV).The blood pharmacokinetics from another 15 tumor-bearing rats was compared with those of non-tumor-bearing rats (III) by injection of In-111-1033-BR96. Results: No statistical difference was detected between the groups regarding the blood pharmacokinetics of rituximab, BR96, or trastuzumab. The pharmacokinetics and biodistribution of In-111-biotin-DOTA-hMN14 exhibited a clear difference compared with others. There were no significant differences in the blood pharmacokinetics of In-111-1033-BR96 between tumor-bearing rats and non-tumor-bearing rats. Conclusions: Different antibodies labeled with the trifunctional chelator 1033 and In-111 did not exhibit different blood pharmacokinetics, which means that the pharmacokinetics could be predicted irrespective of the IgG1 antibody chosen. A small tumor burden did not change the pharmacokinetics of the radioimmunoconjugates.
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| 47. |
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