25 results on '"Terwinghe C"'
Search Results
2. How much do 68Ga-, 177Lu- and 131I-based radiopharmaceuticals contribute to the global radiation exposure of nuclear medicine staff?
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Struelens, L., Aalbersberg, E., Beels, L., Cherbuin, N., D'Asseler, Y., De Monte, F., Lopez Medina, A., del Carmen Riveira Martin, M., Schoonjans, W., Terwinghe, C., Van den Block, S., Vanhavere, F., Zaidi, H., and Schelfhout, V.
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OCCUPATIONAL medicine ,NUCLEAR medicine ,CRYSTALLINE lens ,GLOBAL radiation ,OCCUPATIONAL exposure - Abstract
Background: The radiation exposure of nuclear medicine personnel, especially concerning extremity doses, has been a significant focus over the past two decades. This study addresses the evolving practice of NM, particularly with the rise of radionuclide therapy and theranostic procedures, which involve a variety of radionuclides such as
68 Ga,177 Lu, and131 I. Traditional studies have concentrated on common radioisotopes like99m Tc,18 F, and90 Y, but there is limited data on these radionuclides, which are more and more frequently used. This study, part of the European SINFONIA project, aims to fill this gap by providing new dosimetry data through a multicenter approach. The research monitors extremity doses to hands, eye lens doses, and whole-body doses in nuclear medicine staff handling68 Ga,177 Lu, and131 I. It examines the type of activities performed and the protective measures used. The study extrapolates measured doses to annual doses, comparing them with annual dose limits, and assesses the contribution of these specific procedures to the overall occupational dose of nuclear medicine personnel. Results: Measurements were conducted from November 2020 to August 2023 across nine hospitals. The highest whole-body, eye lens and extremity doses were observed for68 Ga. Average maximum extremity doses, normalized per manipulated activity, were found of 6200 µSv/GBq, 30 µSv/GBq and 260 µSV/GBq for68 Ga,177 Lu and131 I, respectively. Average whole-body doses stayed below 60 µSv/GBq for all 3 isotopes and below 200 µSv/GBq for the eye lens dose. The variation in doses also depends on the task performed. For68 Ga there is a risk of reaching the annual dose limit for skin dose during synthesis and dispensing. Conclusions: This study's measurement campaigns across various European countries have provided new and extensive occupational dosimetry data for nuclear medicine staff handling68 Ga,177 Lu and131 I radiopharmaceuticals. The results indicate that68 Ga contributes significantly to the global occupational dose, despite its relatively low usage compared to other isotopes. Staff working in radiopharmacy hot labs, labeling and dispensing177 Lu contribute less to the finger dose compared to other isotopes. [ABSTRACT FROM AUTHOR]- Published
- 2024
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3. Comparison of diagnostic accuracy of 111In-pentetreotide SPECT and 68Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours
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Van Binnebeek, S., Vanbilloen, B., Baete, K., Terwinghe, C., Koole, M., Mottaghy, F. M., Clement, P. M., Mortelmans, L., Bogaerts, K., Haustermans, K., Nackaerts, K., Van Cutsem, E., Verslype, C., Verbruggen, A., and Deroose, C. M.
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- 2016
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4. An efficient HPLC method for the analysis of isomeric purity of technetium-99m-exametazime and identity confirmation using LC–MS
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Vanderghinste, D., Van Eeckhoudt, M., Terwinghe, C., Mortelmans, L., Bormans, G. M., Verbruggen, A. M., and Vanbilloen, H. P.
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- 2003
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5. Comparison of diagnostic accuracy of 111In-pentetreotide SPECT and 68Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours
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Van Binnebeek, S., primary, Vanbilloen, B., additional, Baete, K., additional, Terwinghe, C., additional, Koole, M., additional, Mottaghy, F. M., additional, Clement, P. M., additional, Mortelmans, L., additional, Bogaerts, K., additional, Haustermans, K., additional, Nackaerts, K., additional, Van Cutsem, E., additional, Verslype, C., additional, Verbruggen, A., additional, and Deroose, C. M., additional
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- 2015
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6. Synthesis of 18F-labelled 2-(4′-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [ 11C]PIB
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Serdons, K., Verduyckt, T., Vanderghinste, D., Cleynhens, J., Borghgraef, P., Vermaelen, P., Terwinghe, C., Leuven, F. Van, Laere, K. Van, Kung, H., Bormans, G., and Verbruggen, A.
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- 2009
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7. Comparison of Diagnostic Accuracy of 111In-Pentetreotide Spect and 68Ga-Dotatoc Pet: a Lesion-By-Lesion Analysis in Prrt-Patients
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Van Binnebeek, S., primary, Vanbilloen, B., additional, Baete, K., additional, Terwinghe, C., additional, Koole, M., additional, Mottaghy, F.M., additional, Clement, P.M., additional, Mortelmans, L., additional, Bogaerts, K., additional, Haustermans, K., additional, Van Cutsem, E., additional, Verslype, C., additional, Verbruggen, A., additional, and Deroose, C.M., additional
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- 2013
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8. Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours.
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Binnebeek, S., Vanbilloen, B., Baete, K., Terwinghe, C., Koole, M., Mottaghy, F., Clement, P., Mortelmans, L., Bogaerts, K., Haustermans, K., Nackaerts, K., Van Cutsem, E., Verslype, C., Verbruggen, A., Deroose, C., Van Binnebeek, S, Mottaghy, F M, Clement, P M, and Deroose, C M
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SINGLE-photon emission computed tomography ,POSITRON emission tomography ,NEUROENDOCRINE tumors ,TUMORS ,CARCINOID ,BONE tumor diagnosis ,BONE tumors ,CLINICAL trials ,COMPARATIVE studies ,COMPUTED tomography ,GALLIUM isotopes ,LIVER tumors ,RESEARCH methodology ,MEDICAL cooperation ,OCTREOTIDE acetate ,RADIOISOTOPES ,RADIOPHARMACEUTICALS ,RESEARCH ,SOMATOSTATIN ,EVALUATION research ,DIAGNOSIS - Abstract
Objectives: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality.Methods: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities.Results: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton.Conclusion: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT.Key Points: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT. [ABSTRACT FROM AUTHOR]- Published
- 2016
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9. Synthesis and evaluation of a 99mTc-BAT-phenylbenzothiazole conjugate as a potential in vivo tracer for visualization of amyloid β
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Serdons, K., Verduyckt, T., Cleynhens, J., Terwinghe, C., Mortelmans, L., Bormans, G., and Verbruggen, A.
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- 2007
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10. Preparation, characterization and biological evaluation of99mTc(CO)3-labelled cyclic polyamines
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Vanbilloen, H. P., primary, Eraets, K., additional, Evens, N., additional, Terwinghe, C., additional, Rattat, D., additional, Bormans, G., additional, Mortelmans, L., additional, and Verbruggen, A. M., additional
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- 2005
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11. O-0006 - Comparison of Diagnostic Accuracy of 111In-Pentetreotide Spect and 68Ga-Dotatoc Pet: a Lesion-By-Lesion Analysis in Prrt-Patients
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Van Binnebeek, S., Vanbilloen, B., Baete, K., Terwinghe, C., Koole, M., Mottaghy, F.M., Clement, P.M., Mortelmans, L., Bogaerts, K., Haustermans, K., Van Cutsem, E., Verslype, C., Verbruggen, A., and Deroose, C.M.
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- 2013
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12. Preparation, characterization and biological evaluation of 99mTc(CO)3-labelled cyclic polyamines.
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Vanbilloen, H. P., Eraets, K., Evens, N., Terwinghe, C., Rattat, D., Bormans, G., Mortelmans, L., and Verbruggen, A. M.
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- 2005
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13. Preparation, characterization and biological evaluation of 99mTc(CO)3‐labelled cyclic polyamines
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Vanbilloen, H. P., Eraets, K., Evens, N., Terwinghe, C., Rattat, D., Bormans, G., Mortelmans, L., and Verbruggen, A. M.
- Abstract
Three cyclic polyamines, namely 1,4,7‐triazacyclononane, 1,4,7,10‐tetraazacyclo‐dodecane (cyclen) and 1,4,8,11‐tetraazacyclotetradecane (cyclam), were evaluated as potential ligands for complexation of a technetium(I) tricarbonyl core. They can be used as bifunctional chelating agents for labelling bioactive compounds. Each of the three ligands forms a positively charged technetium tricarbonyl complex in high yield but heating is required to promote complex formation. The charge of the 99mTc(I)tricarbonyl labelled derivatives was confirmed using electrophoresis, and radio‐LC–MS supports their proposed chemical identity. After i.v. injection in mice, the compounds were rapidly cleared from the blood by the hepatobiliary or urinary pathway depending on their lipophilicity. Copyright © 2005 John Wiley & Sons, Ltd.
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- 2005
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14. Correction to: EANM enabling guide: how to improve the accessibility of clinical dosimetry.
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Gear J, Stokke C, Terwinghe C, Gnesin S, Sandström M, Tran-Gia J, Cremonesi M, Cicone F, Verburg F, Hustinx R, Giovanella L, Herrmann K, and Gabiña PM
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- 2023
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15. EANM enabling guide: how to improve the accessibility of clinical dosimetry.
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Gear J, Stokke C, Terwinghe C, Gnesin S, Sandström M, Tran-Gia J, Cremonesi M, Cicone F, Verburg F, Hustinx R, Giovanella L, Herrmann K, and Gabiña PM
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- Humans, Iodine Radioisotopes, 3-Iodobenzylguanidine, Radiometry methods, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors radiotherapy
- Abstract
Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [
131 I]-NaI for benign thyroid disorders, [177 Lu]-DOTATATE and131 I-mIBG for neuroendocrine tumours and [90 Y]-microspheres for unresectable hepatic carcinoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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16. Best practice for the nuclear medicine technologist in CT-based attenuation correction and calcium score for nuclear cardiology.
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Camoni L, Santos A, Attard M, Mada MO, Pietrzak AK, Rac S, Rep S, Terwinghe C, and Fragoso Costa P
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The use of hybrid systems is increasingly growing in Europe and this is progressively important for the final result of diagnostic tests. As an integral part of the hybrid imaging system, computed tomography (CT) plays a crucial role in myocardial perfusion imaging diagnostics. Throughout Europe, a variety of equipment is available and also different university curricula of the nuclear medicine technologist are observed. Hence, the Technologist Committee of the European Association of Nuclear Medicine proposes to identify, through a bibliographic review, the recommendations for best practice in computed tomography applied to attenuation correction and calcium score in myocardial perfusion imaging, which courses in the set of knowledge, skills, and competencies for nuclear medicine technologists. This document aims at providing recommendations for CT acquisition protocols and CT image optimization in nuclear cardiology.
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- 2020
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17. Technologist Approach to Global Dose Optimization.
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Costa PF, Testanera G, Camoni L, Terwinghe C, Bailey EA, Bolus NE, and Alden TM
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- Heart diagnostic imaging, Humans, Positron Emission Tomography Computed Tomography, Single Photon Emission Computed Tomography Computed Tomography, Nuclear Medicine, Radiation Dosage, Technology, Radiologic
- Abstract
Nuclear medicine technologists are specialized health professionals who cover a wide range of tasks from clinical routine (including image acquisition and processing, radiopharmaceutical dispensing and administration, patient care, and radioprotection tasks) to leading clinical research in the field of nuclear medicine. As a fundamental concern in all radiation sciences applied to medicine, protection of individuals against the harmful effects of ionizing radiation must be constantly revised and applied by the professionals involved in medical exposures. The acknowledgment that nuclear medicine technologists play a prominent role in patient management and several procedural steps, both in diagnostic and in therapeutic nuclear medicine applications, carries the duty to be trained and knowledgeable on the topic of radiation protection and dose optimization. An overview on selected topics related to dose optimization is presented in this article, reflecting the similarities and particularities of dose reduction-related principles, initiatives, and practicalities from a global perspective., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)
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- 2019
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18. Dynamic 68Ga-DOTATOC PET/CT and static image in NET patients. Correlation of parameters during PRRT.
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Van Binnebeek S, Koole M, Terwinghe C, Baete K, Vanbilloen B, Haustermans K, Clement PM, Bogaerts K, Verbruggen A, Nackaerts K, Van Cutsem E, Verslype C, Mottaghy FM, and Deroose CM
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- Aged, Aged, 80 and over, Female, Humans, Image Enhancement methods, Image Interpretation, Computer-Assisted methods, Male, Middle Aged, Molecular Imaging methods, Radiopharmaceuticals pharmacokinetics, Reproducibility of Results, Sensitivity and Specificity, Biomarkers, Tumor metabolism, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors metabolism, Organometallic Compounds pharmacokinetics, Positron Emission Tomography Computed Tomography methods, Receptors, Somatostatin metabolism
- Abstract
Purpose: To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs)., Patients, Methods: 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio)., Results: SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001)., Conclusions: As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.
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- 2016
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19. Individualized dosimetry-based activity reduction of ⁹⁰Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy.
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Van Binnebeek S, Baete K, Vanbilloen B, Terwinghe C, Koole M, Mottaghy FM, Clement PM, Mortelmans L, Haustermans K, Van Cutsem E, Verbruggen A, Bogaerts K, Verslype C, and Deroose CM
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- Adult, Aged, Digestive System Neoplasms diagnostic imaging, Female, Humans, Kidney physiopathology, Kidney radiation effects, Kidney Function Tests, Lung Neoplasms diagnostic imaging, Male, Middle Aged, Neuroendocrine Tumors diagnostic imaging, Octreotide administration & dosage, Octreotide adverse effects, Octreotide therapeutic use, Precision Medicine methods, Radiometry, Radionuclide Imaging, Radiopharmaceuticals administration & dosage, Radiopharmaceuticals adverse effects, Yttrium Radioisotopes administration & dosage, Yttrium Radioisotopes adverse effects, Digestive System Neoplasms radiotherapy, Lung Neoplasms radiotherapy, Neuroendocrine Tumors radiotherapy, Octreotide analogs & derivatives, Radiation Dosage, Radiopharmaceuticals therapeutic use, Yttrium Radioisotopes therapeutic use
- Abstract
Purpose: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney., Methods: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL)., Results: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT., Conclusion: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.
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- 2014
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20. Significant impact of transient deterioration of renal function on dosimetry in PRRT.
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Van Binnebeek S, Baete K, Terwinghe C, Vanbilloen B, Haustermans K, Mortelmans L, Borbath I, Van Cutsem E, Verslype C, Mottaghy FM, Verbruggen A, and Deroose CM
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- Aged, Humans, Intestinal Neoplasms physiopathology, Intestinal Neoplasms radiotherapy, Male, Neuroendocrine Tumors physiopathology, Neuroendocrine Tumors radiotherapy, Octreotide adverse effects, Octreotide analogs & derivatives, Octreotide metabolism, Octreotide therapeutic use, Organometallic Compounds adverse effects, Organometallic Compounds metabolism, Organometallic Compounds therapeutic use, Radiometry, Time Factors, Kidney physiology, Kidney radiation effects, Organs at Risk radiation effects, Radiotherapy adverse effects, Receptors, Peptide metabolism
- Abstract
Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.
- Published
- 2013
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21. Altered biodistribution of somatostatin analogues after first cycle of Peptide receptor radionuclide therapy.
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Van Binnebeek S, Deroose CM, Baete K, Terwinghe C, Vanbilloen B, Koole M, Haustermans K, Mortelmans L, Verslype C, Van Cutsem E, Verbruggen A, and Mottaghy FM
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- Adult, Disease Progression, Female, Humans, Intestinal Neoplasms surgery, Liver Neoplasms radiotherapy, Liver Neoplasms secondary, Lymphatic Metastasis radiotherapy, Magnetic Resonance Imaging methods, Neoplasm Metastasis, Neuroendocrine Tumors surgery, Octreotide therapeutic use, Positron-Emission Tomography methods, Tomography, X-Ray Computed methods, Indium Radioisotopes therapeutic use, Intestinal Neoplasms radiotherapy, Neuroendocrine Tumors radiotherapy, Octreotide analogs & derivatives, Radioisotopes therapeutic use, Receptors, Peptide drug effects, Somatostatin pharmacokinetics, Yttrium Radioisotopes therapeutic use
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- 2011
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22. Synthesis and evaluation of 18F-labeled 2-phenylbenzothiazoles as positron emission tomography imaging agents for amyloid plaques in Alzheimer's disease.
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Serdons K, Terwinghe C, Vermaelen P, Van Laere K, Kung H, Mortelmans L, Bormans G, and Verbruggen A
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- Animals, Benzothiazoles chemistry, Blood-Brain Barrier metabolism, Brain metabolism, Fluorine Radioisotopes, Humans, Male, Mice, Positron-Emission Tomography, Radiopharmaceuticals chemistry, Rats, Rats, Wistar, Structure-Activity Relationship, Thiazoles chemistry, Tissue Distribution, Alzheimer Disease diagnostic imaging, Benzothiazoles chemical synthesis, Brain diagnostic imaging, Plaque, Amyloid diagnostic imaging, Radiopharmaceuticals chemical synthesis, Thiazoles chemical synthesis
- Abstract
Imaging agents targeting amyloid beta (Abeta) may be useful for early diagnosis and follow-up of treatment of patients with Alzheimer's disease (AD). Three of five tested 2-(4'-fluorophenyl)-1,3-benzothiazoles displayed high binding affinities for Abeta plaques in AD human brain homogenates (K(i) between 2.2 and 22.5 nM). They all contained the (18)F-label directly attached to the aromatic ring and were synthesized starting from the nitro precursor. Determination of the partition coefficient, biodistribution studies in normal mice, and in vivo microPET studies in normal rats showed that their initial brain uptake was high and brain washout was fast. The most promising compound [(18)F]5, or 6-methyl-2-(4'-[(18)F]fluorophenyl)-1,3-benzothiazole, seemed to be metabolically stable in the brain, and its plasma radiometabolites, which do not cross the blood-brain barrier, were determined. The preliminary results strongly suggest that this new fluorinated compound is a promising candidate as an Abeta plaque imaging agent for the study of patients with AD.
- Published
- 2009
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23. Synthesis and evaluation of a (99m)Tc-MAMA-propyl-thymidine complex as a potential probe for in vivo visualization of tumor cell proliferation with SPECT.
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Celen S, de Groot T, Balzarini J, Vunckx K, Terwinghe C, Vermaelen P, Van Berckelaer L, Vanbilloen H, Nuyts J, Mortelmans L, Verbruggen A, and Bormans G
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- Animals, Cell Proliferation, Drug Evaluation, Preclinical methods, Feasibility Studies, Metabolic Clearance Rate, Mice, Mice, Nude, Molecular Probe Techniques, Neoplasm Staging, Organ Specificity, Organotechnetium Compounds chemistry, Radiopharmaceuticals chemical synthesis, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, Fibrosarcoma diagnostic imaging, Fibrosarcoma metabolism, Organotechnetium Compounds pharmacokinetics, Tomography, Emission-Computed, Single-Photon methods
- Abstract
Introduction: Cytosolic thymidine kinase (TK1) catalyzes phosphorylation of thymidine to its monophosphate. TK1 activity is closely related with DNA synthesis, and thymidine analogs derivatized with bulky carboranylalkyl groups at the N-3 position were reported to be good substrates for TK1. Accordingly, we have synthesized (99m)Tc-MAMA-propyl-thymidine and evaluated it as a potential tumor tracer., Methods: The bis(S-trityl)-protected MAMA-propyl-thymidine precursor (3-N-[S-trityl-2-mercaptoethyl]-N-[N'-(S-trityl-2-mercaptoethyl)amidoacetyl]-aminopropyl-thymidine) was prepared in three steps, and its structure was confirmed with (1)H NMR and mass spectrometry. Deprotection of the thiols and labeling with (99m)Tc were done in a two-step, one-pot procedure, yielding (99m)Tc-MAMA-propyl-thymidine, which was analyzed with high-performance liquid chromatography, radio-LC-MS analysis (ESI+) and electrophoresis, and its log P was determined. The biodistribution in normal mice was evaluated, and its biodistribution in a radiation-induced fibrosarcoma (RIF) tumor mouse was compared with that of 3'-deoxy-3'-[(18)F] fluorothymidine [(18)F]FLT., Results: (99m)Tc-MAMA-propyl-thymidine was obtained with a radiochemical yield of 70%. Electrophoresis indicated that the complex is uncharged, and its log P was 1.0. The molecular ion mass of the Tc complex was 589 Da, which is compatible with the hypothesized N(2)S(2)-oxotechnetium structure. Tissue distribution showed fast clearance from plasma primarily by the hepatobiliary pathway. Whole-body planar imaging after injection of (99m)Tc-MAMA-propyl-thymidine in an RIF tumor-bearing mouse showed high uptake in the liver and the intestines. No uptake was observed in the tumor, in contrast to the clear uptake observed for [(18)F] FLT visualized with muPET., Conclusions: Although it has been reported that TK1 accepts large substituents at the N-3 position of the thymine ring, the results of this study show that (99m)Tc-MAMA-propyl-thymidine cannot be used as a single photon emission computed tomography tumor tracer, probably because the (99m)Tc-MAMA ligand is too bulky to be tolerated by TK1.
- Published
- 2007
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24. Characterisation and biodistribution of two neutral 99mTc(CO)3 complexes with a tridentate ligand.
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Rattat D, Cleynhens B, Bormans G, Terwinghe C, and Verbruggen A
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- Animals, Brain metabolism, Chromatography, High Pressure Liquid, Ligands, Liver metabolism, Mass Spectrometry, Mice, Organotechnetium Compounds chemical synthesis, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, Organotechnetium Compounds pharmacokinetics, Radiopharmaceuticals chemical synthesis
- Abstract
N-(2-Mercapto-propyl)-1,2-phenylenediamine (MPPDA) and N-beta-aminoethylglycine (AEG) were labelled with 99mTc(CO)3(+) to form the neutral complexes [99mTc(CO)3(MPPDA)] and [99mTc(CO)3(AEG)]. Both complexes were formed in excellent yields and their identity was confirmed by LC-MS. In mice, none of the new tracer agents showed brain uptake. [(99m)Tc(CO)3(MPPDA)] was trapped mainly in the liver and excreted via the hepatobiliary system, whereas [99mTc(CO)3(AEG)] was excreted rapidly via the kidneys to the urine.
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- 2005
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25. Synthesis of 18F-fluoroalkyl-beta-D-glucosides and their evaluation as tracers for sodium-dependent glucose transporters.
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de Groot TJ, Veyhl M, Terwinghe C, Vanden Bempt V, Dupont P, Mortelmans L, Verbruggen AM, Bormans GM, and Koepsell H
- Subjects
- Animals, Fluorine Radioisotopes blood, Glucosides blood, Male, Metabolic Clearance Rate, Mice, Organ Specificity, Radionuclide Imaging, Radiopharmaceuticals blood, Radiopharmaceuticals chemical synthesis, Radiopharmaceuticals pharmacokinetics, Sodium-Glucose Transporter 1, Tissue Distribution, Whole-Body Counting, Xenopus laevis, Fluorine Radioisotopes chemistry, Fluorine Radioisotopes pharmacokinetics, Glucosides chemical synthesis, Glucosides pharmacokinetics, Isotope Labeling methods, Membrane Glycoproteins metabolism, Monosaccharide Transport Proteins metabolism, Oocytes diagnostic imaging, Oocytes metabolism
- Abstract
Unlabelled: Three omega-(18)F-fluoro-n-alkyl-beta-D-glucosides (alkyl = ethyl (5a)), n-butyl (5b), and n-octyl (5c)) were synthesized and evaluated as potential substrates for the sodium/D-glucose cotransporter SGLT1., Methods: The ligands were prepared by (18)F-fluoride displacement of the corresponding tetraacetyl-protected tosylate alkylglucoside precursors in CH(3)CN, followed by hydrolysis of the protective acetate esters with NaOMe/MeOH. Transport of the nonradioactive analogs 5a, 5b, and 5c by the human sodium-D-glucose cotransporter hSGLT1 was characterized in vitro in oocytes of Xenopus laevis that expressed hSGLT1. The biodistribution of the tracers was determined in mice and the presence of metabolites in the blood was investigated. Compound 5a was also evaluated in mice pretreated with phlorizin. The intrarenal distribution of 5a in mice kidney was visualized using autoradiography., Results: The radiochemical yield of 5a, 5b, and 5c was in the range of 8%-15% (end of bombardment) with a total synthesis time of 90 min. The in vitro evaluation after expression of the hSGLT1 showed that 2'-fluoroethyl-beta-D-glucoside (5a) was transported with similar Michaelis-Menten K(m) and V(max) (maximum velocity) values as compared with methyl-alpha-D-glucopyranoside (alpha MDG). The more lipophilic compounds 5b and 5c were not transported but inhibited transport of alpha MDG. In vivo tissue distribution in mice revealed that 5a, 5b, and 5c were cleared mainly by the renal pathway and that 5a showed a significantly higher accumulation in the kidneys and a slower renal excretion as compared with 5b and 5c. Compound 5a was retained mainly in the renal outer medulla containing S3 segments of proximal tubules and the accumulation could be blocked by phlorizin pretreatment. Compound 5c passed the blood-brain barrier to some extent., Conclusion: The data indicate that 2'-(18)F-fluoroethyl-beta-D-glucoside (5a) is a specific tracer of Na(+)-dependent glucose transport that may be used to visualize this transport activity in the S3 segments of renal proximal tubules.
- Published
- 2003
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