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- Heard, J. M., et al.
(författare)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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- Postnov, Andrey, et al.
(författare)
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Radiation Dose of the P-Glycoprotein Tracer 11C-Laniquidar.
- 2013
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 54:12, s. 2101-2103
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to current drug therapy is an important issue in the treatment of epilepsy. Inadequate access of central nervous system drugs to their targets in the brain may be caused by overexpression or overactivity of multidrug transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier. Laniquidar, an inhibitor of P-gp, has been labeled with (11)C for use in PET studies of P-gp expression in humans. Given potential interspecies differences in biodistribution, the purpose of this study was to ensure safe use of (11)C-laniquidar by determining the dosimetry of (11)C-laniquidar using whole-body PET studies.METHODS: Six healthy volunteers were subjected to a series of 10 whole-body PET scans within approximately 70 min. Five blood samples were taken during the series.RESULTS: High uptake of (11)C-laniquidar was seen in liver, spleen, kidneys, and lung, whereas brain uptake was low. The effective dose for (11)C-laniquidar was 4.76 ± 0.13 and 3.69 ± 0.01 μSv·MBq(-1) for women and men, respectively.CONCLUSION: Biodistribution and measured effective dose indicate that (11)C-laniquidar is a safe tracer for PET imaging, with a total dose of about 2 mSv for a brain PET/CT protocol.
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- Rizvi, Saiyada N. F., et al.
(författare)
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Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET
- 2012
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 512-520
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Positron emission tomography (PET) with Zr-89-britumomab tiuxetan can be used to monitor biodistribution of Y-90-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of Zr-89-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of Y-90-ibritumomab tiuxetan influences biodistribution of Zr-89-ibritumomabtiuxetan and whether pre-therapy scout scans with Zr-89-ibritumomab tiuxetan can be used to predict biodistribution of Y-90-ibritumomab tiuxetan and the dose-limiting organ during therapy. Methods: Seven patients with relapsed B-cell non-Hodgkin's lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of similar to 70 MBq Zr-89-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg Y-90-britumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. Results: The highest Y-90 absorbed dose was observed in liver (3.2 +/- 1.8 mGy/MBq) and spleen (2.9 +/- 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 +/- 0.04 mGy/MBq, and the effective dose was 0.87 +/- 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on Zr-89-ibritumomab tiuxetan images was high (Pearson correlation coefficient r=0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r=0.75). Conclusion: Biodistribution of Zr-89-ibritumomab tiuxetan is not influenced by simultaneous therapy with Y-90-ibritumomab tiuxetan, and Zr-89-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using In-111-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.
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- van der Veldt, Astrid A M, et al.
(författare)
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Absolute Quantification of [11C]docetaxel Kinetics in Lung Cancer Patients Using Positron Emission Tomography
- 2011
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 17:14, s. 4814-4824
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([11C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [11C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [11C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration.Experimental Design:Thirty-four lung cancer patients underwent dynamic PET–computed tomography (CT) scans using [11C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [11C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated.Results:Reproducible quantification of [11C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm3) were identified, having a variable net influx rate of [11C]docetaxel (range, 0.0023–0.0229 mL·cm−3·min−1). [11C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = −0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [11C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [11C]docetaxel uptake was related with improved tumor response.Conclusions:Quantification of [11C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [11C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [11C]docetaxel uptake and the effects of comedication on [11C]docetaxel kinetics in tumors.
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