16 results on '"Müller, Cristina"'
Search Results
2. A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides
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Beyer, Darja, Vaccarin, Christian, Deupi, Xavier, Mapanao, Ana Katrina, Cohrs, Susan, Sozzi-Guo, Fan, Grundler, Pascal V., van der Meulen, Nicholas P., Wang, Jinling, Tanriver, Matthias, Bode, Jeffrey W., Schibli, Roger, and Müller, Cristina
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- 2023
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3. Comparison of the dosimetry of scandium-43 and scandium-44 patient organ doses in relation to commonly used gallium-68 for imaging neuroendocrine tumours
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Gomes, Carlos Vinícius, Mendes, Bruno Melo, Paixão, Lucas, Gnesin, Silvano, Müller, Cristina, van der Meulen, Nicholas P., Strobel, Klaus, Fonseca, Telma Cristina Ferreira, and Lima, Thiago Viana Miranda
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- 2024
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4. Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging
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Müller, Cristina, Vermeulen, Christiaan, Johnston, Karl, Köster, Ulli, Schmid, Raffaella, Türler, Andreas, and van der Meulen, Nicholas P.
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- 2016
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5. Folate Receptor-Targeted Radionuclide Imaging Agents
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Müller, Cristina, Schibli, Roger, Jackman, Ann L., editor, and Leamon, Christopher P., editor
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- 2011
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6. 44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations
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Domnanich, Katharina A., Müller, Cristina, Farkas, Renata, Schmid, Raffaella M., Ponsard, Bernard, Schibli, Roger, Türler, Andreas, and van der Meulen, Nicholas P.
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- 2017
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7. Improved PET Imaging of Tumors in Mice Using a Novel 18 F-Folate Conjugate with an Albumin-Binding Entity
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Fischer, Cindy R., Groehn, Viola, Reber, Josefine, Schibli, Roger, Ametamey, Simon M., and Müller, Cristina
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- 2013
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8. Folate-Based Radiotracers for PET Imaging-Update and Perspectives
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Müller, Cristina
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PET ,18F ,Folate receptor ,Folic acid ,44Sc ,152Tb ,68Ga ,Cancer ,Imaging - Abstract
The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant tissue. Therefore, nuclear imaging of FR-positive cancer is of clinical interest for selecting patients who could benefit from innovative therapy concepts based on FR-targeting. Positron emission computed tomography (PET) has become an established technique in clinical routine because it provides an increased spatial resolution and higher sensitivity compared to single photon emission computed tomography (SPECT). Therefore, it is of critical importance to develop folate radiotracers suitable for PET imaging. This review article updates on the design, preparation and pre-clinical investigation of folate derivatives for radiolabeling with radioisotopes for PET. Among those the most relevant radionuclides so far are fluorine-18 (t1/2: 110 min, Eavβ+: 250 keV) and gallium-68 (t1/2: 68 min, Eav β+: 830 keV). Recent results obtained with new PET isotopes such as terbium-152 (t1/2: 17.5 h, Eβ+: 470 keV) or scandium-44 (t1/2: 3.97 h, Eav β+: 632 keV) are also presented and discussed. Current endeavors for clinical implementation of PET agents open new perspectives for identification of FR-positive malignancies in patients., Molecules, 18 (5), ISSN:1420-3049
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- 2013
9. 44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations.
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Domnanich, Katharina A., Müller, Cristina, Farkas, Renata, Schmid, Raffaella M., Ponsard, Bernard, Schibli, Roger, Türler, Andreas, and van der Meulen, Nicholas P.
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POSITRON emission tomography , *PEPTIDES , *LABORATORY mice , *TOMOGRAPHY , *CHELATION - Abstract
Background: Recently, 44 Sc (T1/2 =3.97h,Eβ+av = 632 keV, I = 94.3 %) has emerged as an attractive radiometal candidate for PET imaging using DOTA-functionalized biomolecules. The aim of this study was to investigate the potential of using NODAGA for the coordination of 44Sc. Two pairs of DOTA/NODAGA-derivatized peptides were investigated in vitro and in vivo and the results obtained with 44Sc compared with its 68Ga-labeled counterparts. DOTA-RGD and NODAGA-RGD, as well as DOTA-NOC and NODAGA-NOC, were labeled with 44Sc and 68Ga, respectively. The radiopeptides were investigated with regard to their stability in buffer solution and under metal challenge conditions using Fe3+ and Cu2+. Time-dependent biodistribution studies and PET/CT imaging were performed in U87MG and AR42J tumor-bearing mice. Results: Both RGD- and NOC-based peptides with a DOTA chelator were readily labeled with 44Sc and 68Ga, respectively, and remained stable over at least 4 half-lives of the corresponding radionuclide. In contrast, the labeling of NODAGA-functionalized peptides with 44Sc was more challenging and the resulting radiopeptides were clearly less stable than the DOTA-derivatized matches. 44Sc-NODAGA peptides were clearly more susceptible to metal challenge than 44Sc-DOTA peptides under the same conditions. Instability of 68Ga-labeled peptides was only observed if they were coordinated with a DOTA in the presence of excess Cu2+. Biodistribution data of the 44Sc-labeled peptides were largely comparable with the data obtained with the 68Ga-labeled counterparts. It was only in the liver tissue that the uptake of 68Ga-labeled DOTA compounds was markedly higher than for the 44 Sc-labeled version and this was also visible on PET/CT images. The 44Sc-labeled NODAGA-peptides showed a similar tissue distribution to those of the DOTA peptides without any obvious signs of in vivo instability. Conclusions: Although DOTA revealed to be the preferred chelator for stable coordination of 44Sc, the data presented in this work indicate the possibility of using NODAGA in combination with 44 Sc. In view of a clinical study, thorough investigations will be necessary regarding the labeling conditions and storage solutions in order to guarantee sufficient stability of 44 Sc-labeled NODAGA compounds. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Preclinical in vivo application of Tb-DOTANOC: a radiolanthanide for PET imaging.
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Müller, Cristina, Vermeulen, Christiaan, Johnston, Karl, Köster, Ulli, Schmid, Raffaella, Türler, Andreas, and van der Meulen, Nicholas
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RARE earth metals ,CLASS A metals ,NONFERROUS metals ,POSITRON emission tomography ,DIAGNOSTIC imaging - Abstract
Background: Terbium has attracted the attention of researchers and physicians due to the existence of four medically interesting radionuclides, potentially useful for SPECT and PET imaging, as well as for α- and β-radionuclide therapy. The aim of this study was to produce Tb ( T = 17.5 h, E = 1140 keV) and evaluate it in a preclinical setting in order to demonstrate its potential for PET imaging. For this purpose, DOTANOC was used for targeting the somatostatin receptor in AR42J tumor-bearing mice. Methods: Tb was produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. After separation of Tb using cation exchange chromatography, it was directly employed for radiolabeling of DOTANOC. PET/CT scans were performed with AR42J tumor-bearing mice at different time points after injection of Tb-DOTANOC which was applied at variable molar peptide amounts. Lu-DOTANOC was prepared and used in biodistribution and SPECT/CT imaging studies for comparison with the PET results. Results: After purification, Tb was obtained at activities up to ~600 MBq. Radiolabeling of DOTANOC was achieved at a specific activity of 10 MBq/nmol with a radiochemical purity >98 %. The PET/CT scans of mice allowed visualization of AR42J tumor xenografts and the kidneys, in which the radiopeptide was accumulated. After injection of large peptide amounts, the tumor uptake was reduced as compared to the result after injection of small peptide amounts. PET images of mice, which received Tb-DOTANOC at small peptide amounts, revealed the best tumor-to-kidney ratios. The data obtained with Lu-DOTANOC in biodistribution and SPECT/CT imaging studies confirmed the Tb-based PET results. Conclusions: Production of 30-fold higher quantities of Tb as compared to the previously performed pilot study was feasible. This allowed, for the first time, labeling of a peptide at a reasonable specific activity and subsequent application for in vivo PET imaging. As a β-particle-emitting radiolanthanide, Tb would be of distinct value for clinical application, as it may allow exact prediction of the tissue distribution of therapeutic radiolanthanides. [ABSTRACT FROM AUTHOR]
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- 2016
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11. Imaging quality of 44Sc in comparison with five other PET radionuclides using Derenzo phantoms and preclinical PET.
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Bunka, Maruta, Müller, Cristina, Vermeulen, Christiaan, Haller, Stephanie, Türler, Andreas, Schibli, Roger, and van der Meulen, Nicholas P.
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SCANDIUM , *IMAGING phantoms , *SENSITIVITY analysis , *RADIOISOTOPES , *POLYETHYLENE terephthalate , *CYCLOTRONS - Abstract
PET is the favored nuclear imaging technique because of the high sensitivity and resolution it provides, as well as the possibility for quantification of accumulated radioactivity. 44 Sc ( T 1/2 =3.97 h, Eβ + =632 keV) was recently proposed as a potentially interesting radionuclide for PET. The aim of this study was to investigate the image quality, which can be obtained with 44 Sc, and compare it with five other, frequently employed PET nuclides using Derenzo phantoms and a small-animal PET scanner. The radionuclides were produced at the medical cyclotron at CRS, ETH Zurich ( 11 C, 18 F), at the Injector II research cyclotron at CRS, PSI ( 64 Cu, 89 Zr, 44 Sc), as well as via a generator system ( 68 Ga). Derenzo phantoms, containing solutions of each of these radionuclides, were scanned using a GE Healthcare eXplore VISTA small-animal PET scanner. The image resolution was determined for each nuclide by analysis of the intensity signal using the reconstructed PET data of a hole diameter of 1.3 mm. The image quality of 44 Sc was compared to five frequently-used PET radionuclides. In agreement with the positron range, an increasing relative resolution was determined in the sequence of 68 Ga< 44 Sc< 89 Zr< 11 C< 64 Cu< 18 F. The performance of 44 Sc was in agreement with the theoretical expectations based on the energy of the emitted positrons. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Improved PET Imaging of Tumors in Mice Using a Novel 18 F-Folate Conjugate with an Albumin-Binding Entity.
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Fischer, Cindy R., Groehn, Viola, Reber, Josefine, Schibli, Roger, Ametamey, Simon M., and Müller, Cristina
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POSITRON emission tomography ,CANCER tomography ,MEDICAL imaging systems ,CANCER cells ,LABORATORY mice ,IMAGE quality in imaging systems - Abstract
Purpose: The folate receptor (FR) is a promising target for nuclear imaging due to its overexpression in many different cancer types. A drawback of using folate radioconjugates is the high accumulation of radioactivity in the kidneys. Therefore, the aim of this study was to develop a
18 F-labeled folate conjugate with an albumin-binding entity to enhance the blood circulation time and hence improve the tumor-to-kidney ratio. Procedures: The novel18 F-folate was prepared by conjugation of a18 F-labeled glucose azide to an alkyne-functionalized folate precursor containing an albumin-binding entity via Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radioconjugate was tested in vitro on FR-positive KB tumor cells and by biodistribution and positron emission tomography (PET) imaging studies using KB tumor-bearing mice. Results: The radiosynthesis of the albumin-binding [18 F]fluorodeoxyglucose–folate ([18 F]3) resulted in a radiochemical yield of 1–2 % decay corrected (d.c.) and a radiochemical purity of ≥95 %. The specific activity of [18 F]3 ranged from 20 to 50 GBq/μmol. In vitro experiments revealed FR-specific binding of [18 F]3 to KB tumor cells. In vivo we found an increasing uptake of [18 F]3 into tumor xenografts over time reaching a value of ∼ 15 % injected dose (ID)/g at 4 h post-injection (p.i.). Uptake in the kidneys (∼ 13 % ID/g; 1 h p.i.) was approximately fourfold reduced compared to previously published18 F-labeled folic acid derivatives. An excellent visualization of tumor xenografts with an unprecedentedly high tumor-to-kidney ratio (∼ 1) was obtained by PET imaging. Conclusions: [18 F]3 showed a favorable accumulation in tumor xenografts compared to the same folate conjugate without albumin-binding properties. Moreover, the increased tumor-to-kidney ratios improved the PET imaging quality significantly, in spite of a somewhat higher background radioactivity which was a consequence of the slower blood clearance of [18 F]3. [ABSTRACT FROM AUTHOR]- Published
- 2013
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13. Tumor targeting using 67Ga-DOTA-Bz-folate — investigations of methods to improve the tissue distribution of radiofolates
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Müller, Cristina, Vlahov, Iontcho R., Santhapuram, Hari Krishna R., Leamon, Christopher P., and Schibli, Roger
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FOLIC acid , *TISSUE analysis , *CANCER treatment , *INFLAMMATION , *POSITRON emission tomography , *BIOACCUMULATION , *PHOTON emission , *TOMOGRAPHY - Abstract
Abstract: Introduction: Use of folic acid radioconjugates for folate receptor (FR) targeting is a promising strategy for imaging purposes as well as for potential therapy of cancer and inflammatory diseases due to the frequent FR overexpression found on cancer cells and activated macrophages. Herein, we report on preclinical results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [67Ga]-gallium. Methods: DOTA-Bz-EDA-folate was prepared by conjugation of ethylenediamine-(γ)-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling was carried out with 67GaCl3 according to standard procedures. Biodistribution studies of the tracer were performed in mice bearing FR-positive KB tumor xenografts. The effects on radiofolate biodistribution with coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as well as different routes of administration were likewise investigated. Supportive imaging studies were performed using a small-animal single photon emission computed tomography (SPECT)/CT scanner. Results: 67Ga-DOTA-Bz-EDA-folate showed a high and specific accumulation in tumors (6.30%±0.75% ID/g, 1 h pi and 6.08%±0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted tissues was negligible, but significant accumulation was found in FR-positive kidneys, which resulted in unfavorably low tumor-to-kidney ratios (<0.1). Coadministered amino acids or diuretics did not effectively reduce renal accumulation; in contrast, predosed pemetrexed did significantly reduce kidney uptake (<29% of control values). The SPECT/CT studies confirmed the excellent tumor-to-background contrast of 67Ga-radiofolate and the favorable reduction in kidney uptake (with improved imaging quality) resulting from pemetrexed administration. Conclusion: Conventional methods to reduce kidney uptake of radiofolates fail. However, the novel 67Ga-radiolabeled DOTA-Bz-EDA-folate can effectively be used to image FR-positive cancer and potentially inflammatory diseases. Due to its rapid blood clearance properties, this tracer is also a promising candidate for positron emission tomography imaging if radiolabeled with the short-lived [68Ga]-gallium radionuclide. [Copyright &y& Elsevier]
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- 2011
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14. Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides.
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Lima, Thiago V. M., Gnesin, Silvano, Strobel, Klaus, Pérez, Maria del Sol, Roos, Justus E., Müller, Cristina, and van der Meulen, Nicholas P.
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RADIOISOTOPES ,POSITRON emission tomography ,SCANDIUM ,NUCLEAR medicine - Abstract
Scandium-44 has been proposed as a valuable radionuclide for Positron Emission Tomography (PET). Recently, scandium-43 was introduced as a more favorable option, as it does not emit high-energy γ-radiation; however, its currently employed production method results in a mixture of scandium-43 and scandium-44. The interest in new radionuclides for diagnostic nuclear medicine critically depends on the option for image-based quantification. We aimed to evaluate and compare the quantitative capabilities of scandium-43/scandium-44 in a commercial PET/CT device with respect to more conventional clinical radionuclides (fluorine-18 and gallium-68). With this purpose, we characterized and compared quantitative PET data from a mixture of scandium-43/scandium-44 (~68% scandium-43), scandium-44, fluorine-18 and gallium-68, respectively. A NEMA image-quality phantom was filled with the different radionuclides using clinical-relevant lesion-to-background activity concentration ratios; images were acquired in a Siemens Biograph Vision PET/CT. Quantitative accuracy with scandium-43/scandium-44 in the phantom's background was within 9%, which is in agreement with fluorine-18-based PET standards. Coefficient of variance (COV) was 6.32% and signal recovery in the lesions provided RC
max (recovery coefficient) values of 0.66, 0.90, 1.03, 1.04, 1.12 and 1.11 for lesions of 10-, 13-, 17-, 22-, 28- and 37-mm diameter, respectively. These results are in agreement with EARL reference values for fluorine-18 PET. The results in this work showed that accurate quantitative scandium-43/44 PET/CT is achievable in commercial devices. This may promote the future introduction of scandium-43/44-labelled radiopharmaceuticals into clinical use. [ABSTRACT FROM AUTHOR]- Published
- 2021
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15. Cyclotron production of 44Sc: From bench to bedside.
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van der Meulen, Nicholas P., Bunka, Maruta, Domnanich, Katharina A., Müller, Cristina, Haller, Stephanie, Vermeulen, Christiaan, Türler, Andreas, and Schibli, Roger
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CYCLOTRONS , *POSITRON emission tomography , *RADIONUCLIDE imaging , *ION exchange resins , *TARGETED drug delivery , *RADIOLABELING , *NUCLEAR medicine - Abstract
Introduction 44 Sc, a PET radionuclide, has promising decay characteristics (T 1/2 = 3.97 h, Eβ + av = 632 keV) for nuclear imaging and is an attractive alternative to the short-lived 68 Ga (T 1/2 = 68 min, Eβ + av = 830 keV). The aim of this study was the optimization of the 44 Sc production process at an accelerator, allowing its use for preclinical and clinical PET imaging. Methods 44 CaCO 3 targets were prepared and irradiated with protons (~ 11 MeV) at a beam current of 50 μA for 90 min. 44 Sc was separated from its target material using DGA extraction resin and concentrated using SCX cation exchange resin. Radiolabeling experiments at activities up to 500 MBq and stability tests were performed with DOTANOC by investigating different scavengers, including gentisic acid. Dynamic PET of an AR42J tumor-bearing mouse was performed after injection of 44 Sc-DOTANOC. Results The optimized chemical separation method yielded up to 2 GBq 44 Sc of high radionuclidic purity. In the presence of gentisic acid, radiolabeling of 44 Sc with DOTANOC was achieved with a radiochemical yield of ~ 99% at high specific activity (10 MBq/nmol) and quantities which would allow clinical application. The dynamic PET images visualized increasing uptake of 44 Sc-DOTANOC into AR42J tumors and excretion of radioactivity through the kidneys of the investigated mouse. Conclusions The concept “from-bench-to-bedside” was clearly demonstrated in this extended study using cyclotron-produced 44 Sc. Sufficiently high activities of 44 Sc of excellent radionuclidic purity are obtainable for clinical application, by irradiation of enriched calcium at a cyclotron. This work demonstrates a promising basis for introducing 44 Sc to clinical routine of nuclear imaging using PET. [ABSTRACT FROM AUTHOR]
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- 2015
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16. Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals.
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Haller, Stephanie, Ametamey, Simon M., Schibli, Roger, and Müller, Cristina
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CHICKEN embryos , *ALTERNATIVE medicine , *LABORATORY mice , *RADIOPHARMACEUTICALS , *RADIOLABELING , *PERITONEUM physiology - Abstract
Introduction The chick embryo is an emerging in vivo model in several areas of pre-clinical research including radiopharmaceutical sciences. Herein, it was evaluated as a potential test system for assessing the biodistribution and in vivo stability of radiopharmaceuticals. For this purpose, a number of radiopharmaceuticals labeled with 18 F, 125 I, 99m Tc, and 177 Lu were investigated in the chick embryo and compared with the data obtained in mice. Methods Chick embryos were cultivated ex ovo for 17–19 days before application of the radiopharmaceutical directly into the peritoneum or intravenously using a vein of the chorioallantoic membrane (CAM). At a defined time point after application of radioactivity, the embryos were euthanized by shock-freezing using liquid nitrogen. Afterwards they were separated from residual egg components for post mortem imaging purposes using positron emission tomography (PET) or single photon emission computed tomography (SPECT). Results SPECT images revealed uptake of [ 99m Tc]pertechnetate and [ 125 I]iodide in the thyroid of chick embryos and mice, whereas [ 177 Lu]lutetium, [ 18 F]fluoride and [ 99m Tc]-methylene diphosphonate ([ 99m Tc]-MDP) were accumulated in the bones. [ 99m Tc]-dimercaptosuccinic acid ( 99m Tc-DMSA) and the somatostatin analog [ 177 Lu]-DOTATOC, as well as the folic acid derivative [ 177 Lu]-DOTA-folate showed accumulation in the renal tissue whereas [ 99m Tc]-mebrofenin accumulated in the gall bladder and intestine of both species. In vivo dehalogenation of [ 18 F]fallypride and of the folic acid derivative [ 125 I]iodo-tyrosine-folate was observed in both species. In contrast, the 3′-aza-2′-[ 18 F]fluorofolic acid ([ 18 F]-AzaFol) was stable in the chick embryo as well as in the mouse. Conclusions Our results revealed the same tissue distribution profile and in vivo stability of radiopharmaceuticals in the chick embryo and the mouse. This observation is promising with regard to a potential use of the chick embryo as an inexpensive and simple test model for preclinical screening of novel radiopharmaceuticals. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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