Felix Pareja del Rio

@cun.es

Radiopharmacist / Radiopharmacy Unit (Nuclear Medicine Department)
Clinica Universidad de Navarra

Felix Pareja del Rio


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https://researchid.co/fpareja

RESEARCH, TEACHING, or OTHER INTERESTS

Multidisciplinary
7

Scopus Publications

Scopus Publications

  • Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions
    David Vizarraga, Marina Marcos, Noemi Rotllan, Jesús Martín, David Santos, Mercedes Camacho, Begoña Soto, Lorena Velasco-Reniu, Pablo Guerra, Félix Pareja, María Collantes, Wanlu Wu, Irene Rodríguez-Arce, Luis Serrano, Jaume Piñol, Ignacio Fita, Joan Carles Escolà-Gil
    Nature Communications, 2025
    Mycoplasma pneumoniae (MPN) is a bacterial pathogen that primarily causes atypical pneumonia. It cannot synthesize certain essential lipids and therefore relies on the host for their acquisition to survive. MPN has been detected in increased amounts within ruptured atherosclerotic plaques. In this work, we show that the protein P116 facilitates cholesterol acquisition from LDL, HDL and various cell types. Targeting P116’s C-terminal domain with a monoclonal antibody inhibits cholesterol acquisition and bacterial growth in vitro. Phase contrast epifluorescence microscopy of human arteries reveals that this antibody blocks MPN binding to atherosclerotic lesions ex vivo. Additionally, an MPN chassis injected into hyperlipidemic female mice localizes to the liver and atherosclerotic plaques. Here, we report that P116 plays a role in extracting essential lipids from lipoproteins and host cells and regulates MPN localization to atheromatous plaques. The study highlights MPN’s potential as a tool for targeting atherosclerotic lesions and fatty liver. In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.
  • Comparison of staging using [68Ga]Ga-PSMA-11 PET/CT and histopathological results in intermediate- and high-risk prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection
    J.J. Rosales, V. Betech Antar, F. Mínguez, F. Pareja, F. Guillén, E. Prieto, G. Quincoces, F. Díez Caballero, B. Miñana, J.L. Pérez-Gracia, M. Rodríguez-Fraile
    Revista Espanola De Medicina Nuclear E Imagen Molecular, 2025
  • Phosphatidylserine as a tumor target for CAR-T cell therapy
    Celia Martín-Otal, Inés Sánchez-Moreno, Alvaro Gómez-Morón, Carla Castro, Noelia Casares, Flor Navarro, Marta Gorraiz, Pedro Justicia-Lirio, Felix Pareja, María Collantes, Iván Peñuelas, Mercedes Iñarrairaegui, Bruno Sangro, Isabel Vivas, Marta Larrayoz, Juan Roberto Rodriguez, Felipe Prosper, Sandra Hervas-Stubbs, Noa Martin-Cofreces, Juan Jose Lasarte, Teresa Lozano
    Journal for Immunotherapy of Cancer, 2025
    BackgroundPhosphatidylserine (PS) exposed on apoptotic cells promotes immune clearance of dead cells without inducing inflammation. Conversely, PS exposure on live tumor cells promotes an immunosuppressive tumor microenvironment that hinders antitumor immune responses. After confirming elevated PS levels in various tumor cell lines and cancer tissues, we aimed to investigate its potential as a target antigen for chimeric antigen receptor T cell (CAR-T) therapy.MethodsWe used two different approaches to target PS. First, we employed the adaptor proteins, EDAnnexin or BCMAnnexin comprising annexin V and EDA (extra domain A of fibronectin) or B-cell maturation antigen (BCMA) antigens, to redirect the lytic activity of EDA CAR-T or BCMA CAR-T cells toward PS-expressing tumor cells. In a second approach, we developed an annexin V-based CAR (Anxa CAR-T) to directly recognize PS-positive tumor cells.ResultsThe adaptors proteins EDAnnexin and BCMAnnexin successfully redirected EDA CAR-T or BCMA CAR-T cell activity, leading to an efficient recognition of PS+tumor cells in vitro. However, the established immunological synapse differs significantly from that observed when CAR-T cells recognize the tumor cells directly. In vivo administration of the adaptor proteins, combined with the corresponding CAR-T cells, displayed antitumor activity in mice bearing PS+tumors. Regarding the second approach, Anxa CAR-T cells effectively recognized and killed PS+tumor cells in vitro. Nonetheless, PS exposure on T-cell membranes during T-cell activation impeded efficient Anxa CAR-T cell manufacturing due to fratricide. By optimizing retroviral dose to reduce Anxa CAR expression on the cell membrane, or by using the multikinase inhibitor dasatinib, the fratricide effect was mitigated, enabling successful Anxa CARLow-T cell production. Remarkably, Anxa CARLow-T cells demonstrated antitumor activity in in vivo murine models of PS+hepatocarcinoma and teratocarcinoma. No signs of toxicity were observed after Anxa CAR-T cell administration.ConclusionsPS holds promise as a target antigen for CAR-T cell therapy, underscoring the need to address fratricide as a key challenge in the development of PS-targeting CAR-T cells.
  • Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development
    Jon Ander Simón, Emilia Utomo, Félix Pareja, María Collantes, Gemma Quincoces, Aarón Otero, Margarita Ecay, Juan Domínguez-Robles, Eneko Larrañeta, Iván Peñuelas
    Pharmaceutics, 2023
    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.
  • Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases
    Marta Rua, Jon Ander Simón, María Collantes, Margarita Ecay, José Leiva, Francisco Carmona-Torre, Rocío Ramos, Félix Pareja, Krishna R. Pulagam, Jordi Llop, José Luis Del Pozo, Iván Peñuelas
    Frontiers in Microbiology, 2023
    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[18F] fluoro-D-glucose: [18F]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-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]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 [18F]FDG in vitro. [18F]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 [18F]FPABA. Furthermore, [18F]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.
  • Preclinical safety of negatively charged microspheres (NCMs): Optimization of radiolabeling for in vivo and ex vivo biodistribution studies after topical administration on full-thickness wounds in a rat model
    María Collantes, Claudia Vairo, Álvaro Erhard, Cristina Navas, Silvia Villullas, Margarita Ecay, Félix Pareja, Gemma Quincoces, Garazi Gainza, Iván Peñuelas
    European Journal of Pharmaceutics and Biopharmaceutics, 2022
    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-99 m 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.
  • Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate
    Melibea Berzosa, Alzbeta Nemeskalova, Alba Calvo, Gemma Quincoces, María Collantes, Felix Pareja, Carlos Gamazo, Juan Manuel Irache
    Pharmaceutics, 2022
    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®–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.