Revistas
Revista:
FRONTIERS IN MICROBIOLOGY
ISSN:
1664-302X
Año:
2023
Vol.:
14
Págs.:
1094929
IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[F-18] fluoro-D-glucose: [F-18]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms. MethodsWe tested two specific radiotracers: 2-deoxy-2-[F-18]-fluoro-D-sorbitol ([F-18]FDS) and 2-[F-18]F-rho-aminobenzoic acid ([F-18]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection. Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [F-18]FDG in vitro. [F-18]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [F-18]FPABA. Furthermore, [F-18]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.
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:
NEUROBIOLOGY OF DISEASE
ISSN:
0969-9961
Año:
2022
Vol.:
167
Págs.:
105669
Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
Revista:
MOLECULAR THERAPY. METHODS & CLINICAL DEVELOPMENT
ISSN:
2329-0501
Año:
2022
Vol.:
9
N°:
26
Págs.:
98 - 106
Wilson's disease (WD) is an inherited disorder of copper metabolism associated with mutations in ATP7B gene. We have shown that the administration of an adeno-associated vector (AAV) encoding a mini version of human ATP7B (VTX-801) provides long-term correction of copper metabolism in a murine WD model. In preparation of a future clinical trial, we have evaluated by positron emission tomography (PET) the value of 64Cu biodistribution, excretion pattern, and blood kinetics as pharmacodynamic biomarkers of VTX-801 effects. Six-week-old WD mice were injected intravenously with increasing doses of VTX-801 and 3 weeks or 3 months later with [64Cu]CuCl2. Untreated WD and wild-type (WT) mice were included as controls. Control WD mice showed increased hepatic 64Cu retention, reduced fecal excretion of the radiotracer, and altered 64Cu blood kinetics (BK) compared with WT mice. VTX-801 treatment in WD mice resulted in a significant reduction of hepatic 64Cu accumulation, the restoration of fecal 64Cu excretion, and the correction of 64Cu BK. This study showed that VTX-801 restores physiological copper metabolism in WD mice, confirming the mechanism of action of VTX-801, and demonstrated the translational potential of [64Cu]CuCl2-PET to explore VTX-801 pharmacodynamics in a minimally invasive and sensitive manner in WD patients.
Revista:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Año:
2022
Vol.:
12
N°:
1
Págs.:
18161
The aim was to study the performance of the U-SPECT6/CT E-class system for preclinical imaging, to later demonstrate the viability of simultaneous multi-animal and multi-isotope imaging with reliable quantitative accuracy. The performance of the SPECT was evaluated for two collimators dedicated for mouse (UHS-M) and rat imaging (UHR-RM) in terms of sensitivity, energy resolution, uniformity and spatial resolution. Point sources, hot-rod and uniform phantoms were scanned, and additional tests were carried out to evaluate singular settings such as simultaneous multi-isotope acquisition and imaging with a multi-bed system. For in-vivo evaluation, simultaneous triple-isotope and multi-animal studies were performed on mice. Sensitivity for Tc-99m was 2370 cps/MBq for the UHS-M collimator and 493 cps/MBq for the UHR-RM. Rods of 0.6 mm and 0.9 mm were discernible with the UHS-M and UHR-RM collimators respectively, with optimized reconstruction. Uniformity in low counting conditions has proven to be poor (> 75%). Multi-isotope and multi-bed phantom acquisitions demonstrated accurate quantification. In mice, simultaneous multi-isotope imaging provided the separate distribution of 3 tracers and image quality of the multi-mouse bone scan was adequate. The U-SPECT6/CT E-class has shown good sensitivity and spatial resolution. This system provides quantitative images with suitable image quality for multi-mouse and multi-isotope acquisitions.
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:
CANCERS
ISSN:
2072-6694
Año:
2020
Vol.:
12
N°:
11
Págs.:
31-69
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:
CANCER RESEARCH
ISSN:
0008-5472
Año:
2019
Vol.:
79
N°:
3
Págs.:
625 - 638
Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G(2)-M arrest and apoptosis in mutant KRAS LUAD cells. In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in down-regulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD.
Significance: These findings highlight the prognostic significance of the transcriptional regulator Id1 in KRAS-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.
Revista:
BMC CANCER
ISSN:
1471-2407
Año:
2018
Vol.:
18
N°:
1
Págs.:
1193
BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses.
METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques.
RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01).
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:
JOURNAL OF TRANSLATIONAL MEDICINE
ISSN:
1479-5876
Año:
2017
Vol.:
15
N°:
1
Págs.:
56
PET/CT imaging of 18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.
Revista:
CANCER LETTERS
ISSN:
0304-3835
Año:
2017
Vol.:
402
Págs.:
43 - 51
Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1(+/+) mice and Idl(-/-) mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Idl significantly correlated with vimentin and other EMT-related proteins. Idl loss decreased the levels of vimentin, integrin beta 1, TGF beta 1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. (C) 2017 Elsevier B.V. All rights reserved.
Revista:
NEUROBIOLOGY OF DISEASE
ISSN:
0969-9961
Año:
2015
Vol.:
77
Págs.:
165 - 172
Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague-Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r=0.95, p<0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.
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:
RADIOPROTECCION
ISSN:
1133-1747
Año:
2014
Vol.:
79
Págs.:
26 - 36
La imagen preclínica engloba distintas técnicas de imagen molecular que utilizan radiaciones ionizantes, destacando la tomografía por emisión de fotón único (SPECT), la tomografía de emisión de positrones (PET) y la imagen autorradiográfica. Cada una de ellas utiliza distintas sondas que permiten obtener imágenes de una gran variedad de procesos metabólicos. En ocasiones se emplean junto a equipos de rayos X que permiten obtener imágenes anatómicas. En consecuencia, la investigación en las instalaciones de imagen molecular preclínica deberá realizarse en un contexto en el que se aplique la protección radiológica. De entre los riesgos radiológicos del personal que opera este tipo de instalaciones destaca la irradiación de las manos producida tanto por la administración de los radiotrazadores a los animales como por la manipulación de los mismos, siendo importante el entrenamiento y el uso de los blindajes. El diseño de la instalación radiactiva estará determinado por la actividad que en ella se realice. En particular dependerá tanto de las distintas técnicas de imagen molecular preclínica que se desarrollen como de la relación funcional que la instalación tenga con el resto del centro en el que se encuentre, en particular con el animalario y la unidad de radiofarmacia.
Revista:
CELL TRANSPLANTATION
ISSN:
0963-6897
Año:
2012
Vol.:
21
N°:
5
Págs.:
1023 - 1037
Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived-stromal vascular fraction (SVF) cell transplantation in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP-expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were determined by echocardiography and F-18-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms.
Revista:
PHYSICS IN MEDICINE AND BIOLOGY
ISSN:
0031-9155
Año:
2012
Vol.:
57
N°:
12
Págs.:
3963-80
Tumor volume delineation over positron emission tomography (PET) images is of great interest for proper diagnosis and therapy planning. However, standard segmentation techniques (manual or semi-automated) are operator dependent and time consuming while fully automated procedures are cumbersome or require complex mathematical development. The aim of this study was to segment PET images in a fully automated way by implementing a set of 12 automated thresholding algorithms, classical in the fields of optical character recognition, tissue engineering or non-destructive testing images in high-tech structures. Automated thresholding algorithms select a specific threshold for each image without any a priori spatial information of the segmented object or any special calibration of the tomograph, as opposed to usual thresholding methods for PET. Spherical (18)F-filled objects of different volumes were acquired on clinical PET/CT and on a small animal PET scanner, with three different signal-to-background ratios. Images were segmented with 12 automatic thresholding algorithms and results were compared with the standard segmentation reference, a threshold at 42% of the maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and histogram-shape information, respectively, provided better results that the classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully automated thresholding algorithms can provide better results than classical PET segmentation tools
Revista:
CELL TRANSPLANTATION
ISSN:
0963-6897
Año:
2011
Vol.:
20
N°:
2
Págs.:
259 - 269
There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133(+) cells and multipotent adult progenitor cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133(+) cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days posttransplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133(+)-injected animals. While transplantation of hAC133(+) cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis, and improved muscle regeneration. Incorporation of differentiated MC 133(+) or hMAPC progeny into new vessels was limited; however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-conditioned, but not hAC133(+)-conditioned, media stimulated vascular cell proliferation and prevented myoblast, endothelial, and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133(+) cell and hMAPC transplantation both contribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer term functional improvement.
Revista:
Radiation Measurements
ISSN:
1350-4487
Año:
2011
Vol.:
46
N°:
11
Págs.:
1307 - 1309
This study focuses on the occupational doses of technologists working at an Animal Research Unit using PET radiotracers and on the environmental dose rates produced by the animals (mice, rats and monkeys). In particular, whole body and extremity monitoring is reported and related with the workload. The study shows that doses not only depend on the amount of activity injected but also on the type of animals and radiotracers managed. The extremities, with a great variability of the doses received, are the limiting organs as far as regulatory dose limits for workers are concerned. Mean H¿(10) rates in contact and at 20 cm from the animals, when they are handled by the technologist, range from around 1 mSv/h to 20 ¿Sv/h, respectively.
Revista:
CELL TRANSPLANTATION
ISSN:
0963-6897
Año:
2010
Vol.:
19
N°:
3
Págs.:
313 - 328
The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 10(6) GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and (18)F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 +/- 2.01% to 46.61 +/- 3.7%, p <0.05; MSC: 27.5 +/- 1.28% to 38.8 +/- 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by (18)F-FDG uptake (71.15 +/- 1.27 to 76.31 +/- 1.11, p<0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI.
Nacionales y Regionales
Título:
Nuevas opciones de imagen metabólica en la caracterización de la respuesta inducida por el bloqueo
combinado de anti-PD-1 e Id1 y su correlación con la generación de neontígenos en un modelo de
cáncer de pulmón
Código de expediente:
GNS_53-2021
Investigador principal:
Ignacio Gil Bazo
Financiador:
GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
Convocatoria:
2021 GN Proyectos de Investigación en salud
Fecha de inicio:
23/12/2021
Fecha fin:
22/12/2024
Importe concedido:
78.487,50€
Otros fondos:
-
Título:
Nuevas combinaciones inmunomoduladoras frente al adenocarcinoma de pulmón según el estado mutacional del oncogen KRAS. Estudio de nuevos biomarcadores de respuesta a terapia anti-PD-1
Código de expediente:
PI19/00678
Investigador principal:
Ignacio Gil Bazo
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:
111.320,00€
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:
Nueva estrategia terapéutica para evitar el escape inmune en cáncer de pulmón metastásico mediante el bloqueo combinado de PD-1 e Id1
Código de expediente:
74/2017
Investigador principal:
Ignacio Gil Bazo
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2017 GN SALUD
Fecha de inicio:
01/01/2018
Fecha fin:
15/12/2020
Importe concedido:
90.000,00€
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