Revistas
Revista:
PHARMACEUTICS
ISSN:
1999-4923
Año:
2023
Vol.:
15
N°:
3
Págs.:
843
The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I- took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2022
Vol.:
12
N°:
1
Págs.:
1777
Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy-hypertrophy complex after SIRT. Three groups of 5-8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of Y-90 resin microspheres in rabbits is a reliable animal model to analyse the atrophy-hypertrophy complex and liver damage without toxicity.
Revista:
PHARMACEUTICS
ISSN:
1999-4923
Año:
2022
Vol.:
14
N°:
1
Págs.:
123
Enterotoxigenic Escherichia coli (ETEC) represents a major cause of morbidity and mortality in the human population. In particular, ETEC infections affect children under the age of five from low-middle income countries. However, there is no licensed vaccine against this pathogen. ETEC vaccine development is challenging since this pathotype expresses a wide variety of antigenically diverse virulence factors whose genes can be modified due to ETEC genetic plasticity. To overcome this challenge, we propose the use of outer membrane vesicles (OMVs) isolated from two ETEC clinical strains. In these OMVs, proteomic studies revealed the presence of important immunogens, such as heat-labile toxin, colonization factors, adhesins and mucinases. Furthermore, these vesicles proved to be immunogenic after subcutaneous administration in BALB/c mice. Since ETEC is an enteropathogen, it is necessary to induce both systemic and mucosal immunity. For this purpose, the vesicles, free or encapsulated in zein nanoparticles coated with a Gantrez(R)-mannosamine conjugate, were administered orally. Biodistribution studies showed that the encapsulation of OMVs delayed the transit through the gut. These results were confirmed by in vivo study, in which OMV encapsulation resulted in higher levels of specific antibodies IgG2a. Further studies are needed to evaluate the protection efficacy of this vaccine approach.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN:
0939-6411
Año:
2022
Vol.:
177
Págs.:
61 - 67
Negatively charged microspheres (NCMs) are postulated as a new form of treatment for chronic wounds. Despite the efficacy shown at clinical level, more studies are required to demonstrate their safety and local effect. The objective of the work was to confirm the lack of NCM systemic absorption performing a biodistribution study of the NCMs in an open wound rat animal model. To this end, radiolabeling of NCMs with technetium-99m was optimized and biodistribution studies were performed by in vivo SPEC/CT imaging and ex vivo counting during 24 h after topical administration. The studies were performed on animals treated with a single or repeated dose to study the effect of macrophages during a prolonged treatment. NCM radiolabeling was achieved in a simple, efficient and stable manner with high yield. SPECT/CT images showed that almost all NCMs (about 85 %) remained on the wound for 24 h either after single or multiple administrations. Ex vivo biodistribution studies confirmed that there was no accumulation of NCMs in any organ or tissue except in the wound area, suggesting a lack of absorption. In conclusion, NCMs can be considered safe as local wound treatment since they remain at the administration area.
Revista:
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
ISSN:
1773-2247
Año:
2021
Vol.:
64
Págs.:
101809
The aim of this work was to study the biodistribution of bevacizumab-loaded HSA nanoparticles (NP-Ab) crosslinked with PEG35000 by SPECT/CT in vivo imaging. For this purpose, NP-Abs were prepared by a desolvation process, coated with PEG35000 and radiolabeled with technetium-99 m using a pre-tinning method ([99mTc]TcNP-Ab). The Ab was labeled using [99mTc][Tc(CO)3(H2O)3]+ and used to prepare nanoparticles (NP-[99mTc]TcAb). Particle size was similar in both formulations. Chemical and radiochemical purity of the two nanosystems were >95%. Bevacizumab-labeling conditions were tested by in vitro stability studies. More than 87% of the radiolabeled antibody remained intact for 24 h after incubation with plasma. SPECT/CT imaging of the two nanoparticles was performed in healthy female Wistar rats. Ex vivo gamma counting of selected organs was also carried out in all animals. The results showed different clearance rates of the nanoparticle shell and the antibody, providing valuable information by the use of molecular imaging in the evaluation of drug delivery nanosystems.
Revista:
PHYSICA MEDICA
ISSN:
1120-1797
Año:
2021
Vol.:
84
Págs.:
1 - 9
Purpose: To investigate within phantoms the minimum CT dose allowed for accurate attenuation correction of PET data and to quantify the effective dose reduction when a CT for this purpose is incorporated in the clinical setting.
Methods: The NEMA image quality phantom was scanned within a large parallelepiped container. Twenty-one different CT images were acquired to correct attenuation of PET raw data. Radiation dose and image quality were evaluated. Thirty-one patients with proven multiple myeloma who underwent a dual tracer PET/CT scan were retrospectively reviewed. 18F-fluorodeoxyglucose PET/CT included a diagnostic whole-body low dose CT (WBLDCT: 120 kV-80mAs) and 11C-Methionine PET/CT included a whole-body ultra-low dose CT (WBULDCT) for attenuation correction (100 kV-40mAs). Effective dose and image quality were analysed.
Results: Only the two lowest radiation dose conditions (80 kV-20mAs and 80 kV-10mAs) produced artifacts in CT images that degraded corrected PET images. For all the other conditions (CTDIvol ¿ 0.43 mGy), PET contrast recovery coefficients varied less than ± 1.2%. Patients received a median dose of 6.4 mSv from diagnostic CT and 2.1 mSv from the attenuation correction CT. Despite the worse image quality of this CT, 94.8% of bone lesions were identifiable.
Conclusion: Phantom experiments showed that an ultra-low dose CT can be implemented in PET/CT procedures without any noticeable degradation in the attenuation corrected PET scan. The replacement of the standard CT for this ultra-low dose CT in clinical PET/CT scans involves a significant radiation dose reduction.
Revista:
REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN:
2253-654X
Año:
2020
Vol.:
39
N°:
2
Págs.:
102 - 103
Revista:
REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN:
2253-654X
Año:
2020
Vol.:
39
N°:
2
Págs.:
102 - 103
Autores:
de Arcocha-Torres, M. (Autor de correspondencia); Quincoces, Gemma; Martinez-Lopez, A. L.; et al.
Revista:
REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN:
2253-654X
Año:
2020
Vol.:
39
N°:
4
Págs.:
225 - 232
Revista:
VACCINE
ISSN:
0264-410X
Año:
2019
Vol.:
7
N°:
4
Págs.:
159
Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99mTcO4- radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 g antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA.
Revista:
JOURNAL OF PHARMACEUTICAL SCIENCES
ISSN:
0022-3549
Año:
2019
Vol.:
108
N°:
7
Págs.:
2421 - 2429
Peanut allergy is one of the most prevalent and severe of food allergies with no available cure. The aim of this work was to evaluate the potential of an oral immunotherapy based on the use of a roasted peanut extract encapsulated in nanoparticles with immunoadjuvant properties. For this, a polymer conjugate formed by the covalent binding of mannosamine to the copolymer of methyl vinyl ether and maleic anhydride was first synthetized and characterized. Then, the conjugate was used to prepare nanoparticles with an important capability to diffuse through the mucus layer and reach, in a large extent, the intestinal epithelium, including Peyer's patches. Their immunotherapeutic potential was evaluated in a model of presensitized CD1 mice to peanut. After completing therapy, mice underwent an intraperitoneal challenge with peanut extract. Nanoparticle-treatment was associated with both less serious anaphylaxis symptoms and higher survival rates than control, confirming the protective effect of this formulation against the challenge.
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS. X
ISSN:
2590-1567
Año:
2019
Vol.:
1
Págs.:
100006
The aim of this work was to evaluate the mucus-permeating properties of nanocarriers using zein nanoparticles (NPZ) coated with a Gantrez (R) AN-thiamine conjugate (GT). NPZ were coated by incubation at different GT-to-zein ratios: 2.5% coating with GT (GT-NPZ1), 5% (GT-NPZ2) and 10% (GT-NPZ3). During the process, the GT conjugate formed a polymer layer around the surface of zein nanoparticles. For GT-NPZ2, the thickness of this corona was estimated between 15 and 20 nm. These nanocarriers displayed a more negative zeta potential than uncoated NPZ. The diffusivity of nanoparticles was evaluated in pig intestinal mucus by multiple particle tracking analysis. GT-NPZ2 displayed a 28-fold higher diffusion coefficient within the mucus layer than NPZ particles. These results align with in vivo biodistribution studies in which NPZ displayed a localisation restricted to the mucus layer, whereas GT-NPZ2 were capable of reaching the intestinal epithelium. The gastro-intestinal transit of mucoadhesive (NPZ) and mucus-permeating nanoparticles (GT-NPZ2) was also found to be different. Thus, mucoadhesive nanoparticles displayed a significant accumulation in the stomach of animals, whereas mucus-penetrating nanoparticles appeared to exit the stomach more rapidly to access the small intestine of animals.
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN:
0378-5173
Año:
2019
Vol.:
569
Págs.:
118484
Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
ISSN:
0928-0987
Año:
2019
Vol.:
128
Págs.:
81 - 90
Thiamine-coated nanoparticles were prepared by two different preparative methods and evaluated to compare their mucus-penetrating properties and fate in vivo. The first method of preparation consisted of surface modification of freshly poly(anhydride) nanoparticles (NP) by simple incubation with thiamine (T-NPA). The second procedure focused on the preparation and characterization of a new polymeric conjugate between the poly (anhydride) backbone and thiamine prior the nanoparticle formation (T-NPB). The resulting nanoparticles displayed comparable sizes (about 200 nm) and slightly negative surface charges. For T-NPA, the amount of thiamine associated to the surface of the nanoparticles was 15 mu g/mg. For in vivo studies, nanoparticles were labelled with either Tc-99m or Lumogen (R) Red. T-NPA and T-NPB moved faster from the stomach to the small intestine than naked nanoparticles. Two hours post-administration, for T-NPA and T-NPB, > 30% of the given dose was found in close contact with the intestinal mucosa, compared with a 13.5% for NP. Interestingly, both types of thiamine-coated nanoparticles showed a greater ability to cross the mucus layer and interact with the surface of the intestinal epithelium than NP, which remained adhered in the mucus layer. Four hours post-administration, around 35% of T-NPA and T-NPB were localized in the ileum of animals. Overall, both preparative processes yielded thiamine decorated carriers with similar physico-chemical and biodistribution properties, increasing the versatility of these nanocarriers as oral delivery systems for a number of biologically active compounds.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2018
Vol.:
19
N°:
9
Págs.:
2816
Resveratrol is a naturally occurring polyphenol that provides several health benefits including cardioprotection and cancer prevention. However, its biological activity is limited by a poor bioavailability when taken orally. The aim of this work was to evaluate the capability of casein nanoparticles as oral carriers for resveratrol. Nanoparticles were prepared by a coacervation process, purified and dried by spray-drying. The mean size of nanoparticles was around 200 nm with a resveratrol payload close to 30 ¿g/mg nanoparticle. In vitro studies demonstrated that the resveratrol release from casein nanoparticles was not affected by the pH conditions and followed a zero-order kinetic. When nanoparticles were administered orally to rats, they remained within the gut, displaying an important capability to reach the intestinal epithelium. No evidence of nanoparticle "translocation" were observed. The resveratrol plasma levels were high and sustained for at least 8 h with a similar profile to that observed for the presence of the major metabolite in plasma. The oral bioavailability of resveratrol when loaded in casein nanoparticles was calculated to be 26.5%, 10 times higher than when the polyphenol was administered as oral solution. Finally, a good correlation between in vitro and in vivo data was observed.
Revista:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1619-7070
Año:
2018
Vol.:
45
N°:
Supl. 1
Págs.:
S615
Revista:
THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1824-4785
Año:
2017
Vol.:
61
N°:
4
Págs.:
447 - 455
Background: The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation.
Methods: A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-¿-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells.
Results: Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells.
Conclusions: Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
ISSN:
0939-6411
Año:
2015
Vol.:
97
N°:
A
Págs.:
280 - 289
The aim of this work was to investigate the mucus-permeating properties of poly(ethyleneglycol)-coated nanoparticles prepared from the copolymer of methyl vinyl ether and maleic anhydride (Gantrez® AN) after oral administration in rats. Nanoparticles were ¿decorated¿ with PEGs of different molecular masses (PEG2000, PEG6000 and PEG10000) at a PEG-to-polymer ratio of 0.125. All the PEG-coated nanoparticles displayed a mean size of ~150 nm, slightly negative ¿ values and a ¿brush¿ conformation as determined from the calculation of the PEG density. For in vivo studies, nanoparticles were labelled with either 99mTc or fluorescent tags. Naked nanoparticles displayed a higher ability to interact with the mucosa of the stomach than with the small intestine. However, these interactions were restricted to the mucus layer covering the epithelial surface, as visualised by fluorescence microscopy. On the contrary, PEG-coated nanoparticles moved rapidly to the intestine, as determined by imaging, and, then, were capable to develop important interactions with the mucosa, reaching the surface of the epithelium. These mucus permeating properties were more intense for nanoparticles coated with PEG2000 or PEG6000 than with PEG10000. However, the capability of nanocarriers to develop adhesive interactions within the mucosa decreased when prepared at excessive PEG densities.
Revista:
EJNMMI RESEARCH
ISSN:
2191-219X
Año:
2015
Vol.:
15
N°:
1
Págs.:
70
Background: [F-18]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99)mTc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [F-18]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs.
Methods: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 +/- 0.05 MBq/kg of [F-18]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [F-18]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model.
Results: [F-18]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the orga
Revista:
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
ISSN:
1773-2247
Año:
2015
Vol.:
30
N°:
B
Págs.:
450 - 457
The aim of this work was to prepare and evaluate the capability of zein nanoparticles for oral drug delivery. More particularly, in this work, the ability of these nanoparticles to improve the oral bioavailability of folic acid is reported. The nanoparticles were prepared by a desolvation process, followed by purification via ultrafiltration and drying in a spray-drier apparatus. The resulting nanoparticles displayed a mean size close to 200 nm with negative zeta potential and a payload of 54 ¿g folic acid per mg nanoparticle. From the in vitro release studies, it was observed that folic acid was only released from nanoparticles in simulated intestinal conditions. In vivo biodistribution studies, with radiolabelled or fluorescently marked nanoparticles, revealed that nanoparticles remained within the gut and were capable of interacting with the protective mucus layer of the jejunum. For the pharmacokinetic study, folic acid was orally administered to rats as a single dose of 1 mg/kg.
The relatively oral bioavailability of folic acid, when encapsulated in zein nanoparticles, was around 70%: two-times higher than the value obtained with an aqueous solution of the vitamin. This fact might be explained by the mucoadhesive properties of these nanoparticles.
Revista:
REV ESP MED NUCL IMAGEN MOL
ISSN:
2253-654X
Año:
2013
Vol.:
32
N°:
2
Págs.:
92 - 97
Purpose: To optimize radiolabeling with (99m)Tc of mannosylated Gantrez(®) nanoparticles loaded with the Brucella Ovis antigen (Man-NP-HS) and to carry out biodistribution studies in mice after ocular administration of the nanoparticles.
Material and methods: Man-NP-HS nanoparticles were prepared by the solvent displacement method. They were purified, lyophilized and characterized. Following this, they were radiolabeled with 74 MBq of (99m)TcO4(-) previously reduced with an acidic stannous chloride solution, working in absence of oxygen and at a final pH of 4. Radiolabeling yield was evaluated by TLC. Biodistribution studies were carried out in mice after ocular administration of the formulation and control of free (99m)TcO4(-). To do so, the animals were humanely killed at 2 and 24hours after the ocular administration and activity in organs was measured in a Gamma counter.
Results: Radiolabeling yield obtained was greater than 90%. Biodistribution studies of (99m)Tc-Man-NP-HS showed radioactivity accumulated at 2 and 24hours in nasal and ocular mucosa and gastrointestinal tract, in contrast to biodistribution of free (99m)TcO4(-) that remained concentrated in the skin around the eye and gastrointestinal tract.
Conclusion: Biodistribution studies of (99m)Tc-Man-NP-HS after ocular instillation have made it possible to demonstrate its biodistribution in nasal mucosa and gastrointestinal tract. This characteristic is essential as an antigenic delivery system throughout the ocular mucosa. This, together with its elevated immune response, effective protection and intrinsic avirulence make them a suitable anti-Brucella vaccine candidate.
Revista:
BRAIN
ISSN:
0006-8950
Año:
2012
Vol.:
135
Págs.:
2817-25
Neuronal loss in Alzheimer's disease, a better correlate of cognitive impairment than amyloid deposition, is currently gauged by the degree of regional atrophy. However, functional markers, such as GABA(A) receptor density, a marker of neuronal integrity, could be more sensitive. In post-mortem hippocampus, GABA(A) messenger RNA expression is reduced even in mild cognitive impairment. We measured whole-brain GABA(A) binding potential in vivo using [(11)C]-flumazenil positron emission tomography and compared GABA(A) binding with metabolic and volumetric measurements. For this purpose, we studied 12 subjects, six patients with early Alzheimer's disease and six healthy controls, with [(11)C]-flumazenil and [(18)F]-fluorodeoxyglucose positron emission tomography, as well as with high-resolution magnetic resonance imaging. Data were evaluated with both voxel-based parametric methods and volume of interest methods. We found that in early Alzheimer's disease, with voxel-based analysis, [(11)C]-flumazenil binding was decreased in infero-medial temporal cortex, retrosplenial cortex and posterior perisylvian regions. Inter-group differences reached corrected significance when using an arterial input function. Metabolism measured with positron emission tomography and volumetric measurements obtained with magnetic resonance imaging showed changes in regions affected in early Alzheimer's disease, but, unlike with [(11)C]-flumazenil binding and probably due to sample size, the voxel-based findings failed to reach corrected significance in any region of the brain. With volume of interest analysis, hippocampi and posterior cingulate gyrus showed decreased [(11)C]-flumazenil binding. In addition, [(11)C]-flumazenil hippocampal binding correlated with memory performance. Remarkably, [(11)C]-flumazenil binding was decreased precisely in the regions showing the greatest degree of neuronal loss in post-mortem studies of early Alzheimer's disease. From these data, we conclude that [(11)C]-flumazenil binding could be a useful marker of neuronal loss in early Alzheimer's disease
Revista:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1619-7070
Año:
2012
Vol.:
39
N°:
5
Págs.:
771 - 781
PURPOSE:
The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade.
METHODS:
We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately.
RESULTS:
Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p¿<¿0.001, ¿¿=¿0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5).
CONCLUSION:
The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.
Revista:
Molecular Imaging and Biology
ISSN:
1536-1632
Año:
2011
Vol.:
13
N°:
6
Págs.:
1215 - 1223
Purpose: Study by molecular imaging the biodistribution of poly(anhydride) nanoparticles after oral administration.
Procedures: Poly (anhydride) nanoparticles (NP) and cyclodextrin-tagged nanoparticles (CD-NP) were radiolabelled with Tc-99m. Radiochemical purity was measured with a double-solvent chromatography system and the absence of undesirable components was confirmed by size and polydispersion measurement of the technetium-labelled nanoparticles by photon correlation spectroscopy. Single photon emission computed tomography (SPECT) fused computed tomography (CT) in vivo molecular imaging was used for biodistribution studies in small animals.
Results: SPECT-CT images revealed activity only in the gastrointestinal tract. Thirteen percent of the given dose of CD-NP and 3% of the given dose of conventional NP were found in the stomach at 8 h.
Conclusion: No evidence of translocation or distribution out of gastrointestinal tract was found. CD-NP moved significantly more slowly inside the gut than conventional NP, probably due to their physico-chemical structure that allows stronger interactions with the gut mucosa.
Revista:
Applied Radiation and Isotopes
ISSN:
0969-8043
Año:
2010
Vol.:
68
N°:
12
Págs.:
2298 - 301
Revista:
Molecular Imaging and Biology
ISSN:
1536-1632
Año:
2010
Vol.:
12
N°:
2
Págs.:
210 - 217
Revista:
Computers in Biology and Medicine
ISSN:
0010-4825
Año:
2010
Vol.:
40
N°:
1
Págs.:
75 - 80
Nacionales y Regionales
Título:
Desarrollo de nuevas terapias antitumorales de elevada eficacia y especificidad y baja toxicidad para administración oral
Código de expediente:
RTC-2014-2589-1
Investigador principal:
José Ignacio Fernández de Trocóniz Fernández
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2014 MINECO Retos Colaboración
Fecha de inicio:
29/01/2014
Fecha fin:
30/06/2018
Importe concedido:
202.435,00€
Otros fondos:
-
Título:
Desarrollo de una inmunoterapia oral basada en nanopartículas para el tratamiento de alergias alimentarias
Código de expediente:
RTC-2015-3826-1
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2015 MINECORETOS-COLABORACION
Fecha de inicio:
23/02/2015
Fecha fin:
30/06/2019
Importe concedido:
132.700,00€
Otros fondos:
-
Título:
Probióticos como agentes inmunomoduladores de vacunas
Código de expediente:
GN2022/04
Investigador principal:
Carlos Manuel Gamazo de la Rasilla
Financiador:
GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
Convocatoria:
2022 GN Proyectos de Investigación en salud
Fecha de inicio:
22/12/2022
Fecha fin:
21/12/2025
Importe concedido:
79.119,13€
Otros fondos:
-
Título:
NANO-IMMUNOTHERAPY: INTRACELLULAR TARGETING OF CANCER CELLS AND TAMS
Código de expediente:
PCIN-2017-017
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2017 MINECO APCIN
Fecha de inicio:
01/10/2017
Fecha fin:
30/06/2021
Importe concedido:
100.000,00€
Otros fondos:
-
Título:
Nueva terapia fágica frente a infecciones de E. coli en humanos (ANTI-COLI)
Código de expediente:
0011-1365-2020-000279
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2020 GN I+D Transferencia del conocimiento (empresas)
Fecha de inicio:
01/04/2020
Fecha fin:
31/07/2022
Importe concedido:
224.058,73€
Otros fondos:
Fondos FEDER
Título:
Imagen in vivo de la biodistribución de nanovacunas radiomarcadas de administración oral para enfermedades infecciosas
(INNAVACORID)
Código de expediente:
PI21/01003
Investigador principal:
María Collantes Martínez, Iván Peñuelas Sánchez
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2021 AES Proyectos de investigación
Fecha de inicio:
01/01/2022
Fecha fin:
31/12/2024
Importe concedido:
117.370,00€
Otros fondos:
Fondos FEDER
Título:
Correlación entre el depósito de tau, la disfunción neuronal y el fenotipo clínico en pacientes con Parálisis Progresiva Primaria: estudios de neuroimagen e Histología.
Código de expediente:
PI20/00245
Investigador principal:
Javier Ignacio Arbizu Lostao
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2020 AES Proyectos de investigación
Fecha de inicio:
01/01/2021
Fecha fin:
31/12/2023
Importe concedido:
95.590,00€
Otros fondos:
Fondos FEDER
Título:
Vacuna no-parental frente a infecciones por Escherichia coli enteroxigénicas
Código de expediente:
PI19/00416
Investigador principal:
Carlos Manuel Gamazo de la Rasilla, Juan Manuel Irache Garreta
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2019 AES Proyectos de investigación
Fecha de inicio:
01/01/2020
Fecha fin:
31/12/2022
Importe concedido:
147.620,00€
Otros fondos:
Fondos FEDER
Título:
Desarrollo de nuevos compuestos radiofluorados para el diagnóstico in vivo de infección prótesica articular mediante imagen PET (DIPAPET)
Código de expediente:
PI17/00873
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
AES2017 PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2018
Fecha fin:
31/12/2021
Importe concedido:
93.170,00€
Otros fondos:
Fondos FEDER
Título:
Evaluación de 18F-FDG, 11C-MET y 11C-COL para la detección de infiltración tumoral en Mieloma Múltiple (MM): Estudio traslacional en modelos preclínico y clínico en pacientes (MIELOMAPET)
Código de expediente:
PI16/00225
Investigador principal:
María José García Velloso, Patricia Maiso Castellanos
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2016 AES PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2017
Fecha fin:
31/12/2019
Importe concedido:
74.415,00€
Otros fondos:
Fondos FEDER