Los trabajos han dado como resultado el desarrollo y validación del primer sistema trimodal preclínico que integra simultáneamente PET, resonancia magnética (MRI) y ultrasonido focalizado (FUS). El inserto PET, basado en cristales monolíticos LYSO con capacidad de detección de profundidad de interacción (DOI), ha demostrado un rendimiento sobresaliente: resolución espacial submilimétrica (~0.9 mm), sensibilidad pico del 3.8% y excelente calidad de imagen, comparable con los sistemas PET preclínicos más avanzados.
Figura 1. Resumen de la evaluación del sistema PET, incluyendo los resultados de resolución espacial, sensibilidad, NECR, y de los fantomas IQ y microDerenzo.
Se realizaron pruebas de compatibilidad simultánea con un sistema MRI de bajo campo y un dispositivo FUS personalizado. Mediante la utilización de un fantoma especialmente diseñado, se demostró que el sistema puede adquirir imágenes PET y MRI durante la sonicación FUS sin degradación significativa de la señal.
Figura 2. Imágenes reconstruidas de la adquisición simultánea con el inserto PET, la MRI de bajo campo y el sistema FUS. (a) Vista transversal de la composición del fantoma en dos instantes temporales: antes (1 min, 20 °C) y después (30 min, 40 °C) de la aplicación de FUS. (b) Imágenes de MRI del fantoma en esos dos tiempos. (c) Reconstrucciones PET correspondientes a los mismos instantes. (d) Perfiles de actividad extraídos de las imágenes PET a 1, 15 y 30 minutos, mostrando la mezcla del radiotrazador con la gelatina.
Este avance abre nuevas posibilidades en investigación biomédica, incluyendo neuromodulación, inmunoterapia y administración localizada de fármacos, y sienta las bases para futuras aplicaciones clínicas en humanos.
Además, se ha desarrollado nuevas nanomedicinas de Gemcitabina basadas en redes covalentes orgánicas (COFs), a las que se les incorpora una molécula directora. Estos nanofármacos han demostrado una elevada eficacia antitumoral contra células de cáncer de vejiga músculo-infiltrante (MIBC), y a su vez presentan alta biocompatibilidad, habiendo mostrando una amplia ventana terapéutica en los ensayos preclínicos in vitro e in vivo.
La combinación del tratamiento farmacológico basados en nanomedicinas de Gemcitabina con el sistema de imagen trimodal PET-MRI-FUS ofrece un potencial enorme para el seguimiento de los tratamientos anticancerígenos con alta precisión.
Publicaciones:
Evaluation of a PET Insert for Trimodal Imaging: A Step Towards PET/MRI-guided Focused Ultrasound. F. López-Berenguer, A. González Montoro, M. Freire, A. J. González Martínez… Submitted to Transactions Medical Imaging, January 2025.
First validation of a trimodal imaging and therapy system:PET-FUS-MR. F.López-Berenguer, A.González Montoro, M.Freire, A González Martínez… DIO:10.1109/NSS/MIC/RTSD57108.2024.10657031. Published in 2024 IEEE Nuclear Science Symposium (NSS), Medical Imaging Conference (MIC) and Room Temperature Semiconductor Detector Conference (RTSD).
Prostate cancer chemotherapy by intratumoral administration of docetaxel-mesoporous silica nanomedicines. Eva Rivero-Buceta, Adrian Bernal-Gomez, Carla Vidaurre-Agut, Eric Lopez Moncholi, Jose María Benlloch, Victoria Moreno Manzano, Cesar David Vera Donoso, Pablo Botella. International Journal of Pharmaceutics 664 (2024) 124623. DOI: 10.1016/j.ijpharm.2024.124623 .
Preparation of monodispersed mesoporous silica nanoparticles by spray drying. Lucia Gomez, Eva Maria Rivero-Buceta, Carla Vidaurre-Agut, Pablo Botella. Microporous and Mesoporous Materials (2025). In revision (manuscript MICMAT-D-25-00082).
Elliptical Halbach magnet and gradient modules for low-field portable MRI. F. Galve, E. Pallás, P. García-Cristóbal, T. Guallart-Naval, P. Martínez, J. M. Algarín, J. Borreguero, R. Bosch, F. Juan-Lloris, J. M. Benlloch and J. Alonso. Submitted to Physics for Medicine and Biology, (2024).
Zero-echo-time sequences for short T2* imaging in highly inhomogeneous fields. J. Borreguero, F. Galve, J.M. Algarín and J. Alonso. Publication in preparation, (2024).
MaRCoS, an open-source electronic control system for low-field MRI. V. Negnevitsky, Y. Vives-Gilabert, J.M. Algarín, L. Craven-Brightman, R. Pellicer-Guridi, T. O’Reilly, J.P. Stockmann, A. Webb, J. Alonso, B. Menküc. Journal of Magnetic Resonance. 107424 (2023). DOI: https://doi.org/10.1016/j.jmr.2023.107424. Public preprint in https://arxiv.org/abs/2208.01616.
MaRGA: a Graphical and Application Interface for MaRCoS. J.M. Algarín, T. Guallart-Naval, J. Borreguero, F. Galve, J. Alonso. Accepted by Journal of Magnetic Resonance, (2024). Public preprint in https://arxiv.org/abs/2312.08711.
Light-Activated Controlled Release of Camptothecin by Engineering Porous Materials: The Ship in a Bottle Concept in Drug Delivery. Eva Rivero Buceta, Mirela E. Encheva, Bradley Cech, Eduardo Fernandez, Germán Sastre, Christopher C. Landry, Pablo Botella. Nanoscale 2023, 25, 12506-12517. Cover Article.
Position estimation using neural networks in semi-monolithic PET detectors. M Freire, J Barrio, N Cucarella, C Valladares, A Gonzalez-Montoro, C de Alfonso, J. M. Benlloch and A. J. Gonzalez
Physics in Medicine & Biology., 67 (24), 245011, Dec 2022
Performance evaluation of side-by-side optically coupled monolithic LYSO crystals. Marta Freire, Sara Echegoyen, Andrea Gonzalez-Montoro, Filomeno Sanchez, and Antonio J. Gonzalez
Medical Physics., accepted, early access, July 2022
MR compatibility assessment of the edgeless preclinical PET insert: ScintoTube. Andrea González-Montoro et al., 2023 IEEE Nuclear Science Symposium, Medical Imaging Conference and International Symposium on Room-Temperature Semiconductor Detectors (NSS MIC RTSD), Vancouver, BC, Canada, 2023, pp. 1-2, doi: 10.1109/NSSMICRTSD49126.2023.10338645.
Reducing edge effects in semi-monolithic PET detectors using optical barriers: a simulation study, G. Cañizares, M. Freire, A. González-Montoro, H. Sabet, P. Bruyndonckx and A. J. Gonzalez, 2023 IEEE Nuclear Science Symposium, Medical Imaging Conference and International Symposium on Room-Temperature Semiconductor Detectors (NSS MIC RTSD), Vancouver, BC, Canada, 2023, pp. 1-1, doi: 10.1109/NSSMICRTSD49126.2023.10338558.
Methods to design and evaluate transcranial ultrasonic lenses using acoustic holography. D. Andrés, A. Carrión, F. Camarena, N. Jiménez. Physical Review Applied 20, 044071 (2023).
Conferencias, presentaciones y seminarios:
Reaching new horizons in pre-clinical imaging:trimodal PET-FUS-MR technology. Andrea González-Montoro (Institute for instrumentation in Molecular Imaging, I3M-CSIC). PSMR2024 10th Conference on PET, SPECT, and MR Multimodal Technologies, Total Body and Fast timing in Medial Imaging. 19-13 de mayo de 2024 La Biodola, Isola D’Elba.
A hybrid Low-Cost MR-PET technology with holographic ultrasound capabilities. Teresa Guallart Naval (Institute for instrumentation in Molecular Imaging, I3M-CSIC). ISMRM Iberian Chapter 4th Annual Meeting of the ISMRM Iberian Chapter.2-3 July 2024 Porto.
A hybrid Low-Cost MR-PET technology with holographic ultrasound capabilities. Teresa Guallart Naval (Institute for instrumentation in Molecular Imaging, I3M-CSIC). ESMRMB 2024 40th Annual Scientifc Meeting .2-5 October Barcelona.
First Validation of a Trimodal Imaging and Therapy System: PET-FUS-MR. Andrea González-Montoro (Institute for instrumentation in Molecular Imaging, I3M-CSIC). IEEE NSS/MIC conference, Tampa, Florida, USA. 29 October 2024.
Validation of a Trimodal Imaging and Therapy System: PET-FUS-MR. Fernando Lopez-Berenguer (Institute for instrumentation in Molecular Imaging, I3M-CSIC). Bienal de Física, San Sebastian, España. Julio 2024.
Mesoporous silica nanoparticles with very large pores for the light -activated controlled released of camptothecin. E. Rivero-Buceta, M.E. Encheva, B. Cech, E. Fernandez, G. Sastre, C.C. Landry, P. Botella. 17th European Symposium on Controlled Drug Delivery, Egmond aan Zee, The Netherlands. April 2024.
Production of mesoporous silica nanoparticle through spray drying. L. Gomez, E. Rivero-Buceta, P. Botella. 17th European Symposium on Controlled Drug Delivery, Egmond aan Zee, The Netherlands. April 2024.
Porphyrin free organic contrast agents for photoacoustic imaging. I. Pi-Martin, C.M. Vidaurre-Agut, A. Cebrecos, J.J. Garcia-Garrigos, N. Jimenez, J.M. Benllcoh, P. Botella, F. Camarena. 22st International Conference on Photoacoustics and Photothermal Phenomena, Coimbra, Portugal, July 2024.
Light-activated release of camptothecin in engineered porous materials as drug delivery system. S- Domingo Pelegrí, J. Lagares, E. Rivero-Buceta, M.E. Encheva, B. Cech, E. Fernandez, G. Sastre, C. C. Landry, P. Botella. Nanomaterials Applied to Life Science, Granada, Spain, February 2024.
AG5 is a novel non-steroidal anti-inflammatory and immune regulator that minimizes Cytokine Release Syndrome and preserves innate immunity. P. Botella-Asunción, E. Rivero-Buceta, C. Vidaurre-Agut, J.M. Quesada-Gómez, F. Prosper, J. San Miguel, A. Pineda-Lucena, J.M. Benlloch. 4th Swedish Medicinal Chemistry Symposium, Stockholm, Sweden, April 2024.
J. Alonso et al., Slice-selective Zero Echo Time imaging of ultra-short T2 tissues, ISMRM Workshop on data sampling and image reconstruction (Sedona, Arizona, Jan 2023)
J.M. Algarín et al., Muscle volumetry from low-field scans and its relation to performance in physical activities, ISMRM 2023 annual meeting (Toronto, Canada, May 2023)
J.M. Algarín et al., Portable MRI for major sporting events -a case study on the Moto GP World Championship, ISMRM 2023 annual meeting (Toronto, Canada, May 2023)
J. Borreguero et al., Slice-selective Zero Echo Time imaging of ultra-short T2 tissues, ISMRM 2023 annual meeting (Toronto, Canada, May 2023)
J. Alonso, MRI for everybody, everywhere, ISMRM Iberian Chapter annual meeting (Valladolid, Spain, Jun 2023)
J. Borreguero et al., Prepolarized MRI of soft and hard biological tissues, ISMRM Iberian Chapter annual meeting (Valladolid, Spain, Jun 2023)
J.M. Algarín et al., Low-field MRI gastrocnemius segmentation and correlation with physical performance on sportspeople, ISMRM Iberian Chapter annual meeting (Valladolid, Spain, Jun 2023)
T. Guallart-Naval et al., Portable MRI for major sporting events – a case study on the MotoGP World Championship, ISMRM Iberian Chapter annual meeting (Valladolid, Spain, Jun 2023)
J. Borreguero et al., Slice-selective Zero Echo Time imaging of ultra-short T2 tissues, ESMRMB annual meeting (Basel, Switzerland, Oct 2023)
J.M. Algarín et al., New graphical user interface and gradient control electronics for the MaRCoS open-source console, ESMRMB annual meeting (Basel, Switzerland, Oct 2023)
J.M. Algarín et al., Low-field MRI gastrocnemius segmentation and correlation with physical performance on sportspeople, ESMRMB annual meeting (Basel, Switzerland, Oct 2023)
T. Guallart-Naval et al., Portable MRI for major sporting events – A case study on the MotoGP world championship, ESMRMB annual meeting (Basel, Switzerland, Oct 2023)
T. Guallart-Naval et al., Portable MRI indoors, outdoors and at home, ESMRMB annual meeting (Basel, Switzerland, Oct 2023)
J. Alonso, MRI for everybody, everywhere, Libre hub seminar (Santiago de Chile, Chile, Oct 2023)
J. Borreguero et al., Building a low-field dental MRI scanner, IV Jornadas RSEF / IFIMED (Sevilla, Spain, Nov 2023)
T. Guallart-Naval et al., Portable MRI indoors, outdoors, at home and for major sporting events, IV Jornadas RSEF / IFIMED (Sevilla, Spain, Nov 2023)
J.M. Algarín et al., New graphical user interface and gradient control electronics for the MaRCoS open-source console, MRI Together Workshop (online, Dec 2023)
T. Guallart-Naval et al., MRI for everybody, everywhere, Invited talk at Universidad Nacional Autónoma de México (Ciudad de México, México, Dec 2023)
E. Rivero, M. Evgenieva, B. Cech, E. Fernandez, G. Sastre, C.C. Landry, P. Botella. Controlled Release of Camptothecin by Light-Activation in Engineered Porous Materials. BioNanoMed 2023. Graz (Austria) 12-14 April 2023. Oral presentation.
E. Rivero-Buceta1 A. Bernal, E. López, V. Moreno, C.D. Vera-Donoso, J.M. Benlloch, and P. Botella. Prostate cancer therapy study in xenografts by intratumor administration of docetaxel nanomedicines. BioNanoMed 2023. Graz (Austria) 12-14 April 2023. Poster presentation.
Macchione, Micaela A., Castro Luna, Sofía B., Botella Pablo, Strumia, Miriam C. Nanogeles híbridos basados en sílica mesoporosa, nanopartículas de oro y polímeros termo-responsivos. XXIII Congreso Argentino de Fisicoquímica y Química Orgánica (CAFQI). El Calafate (Argentina) 11-14 April 2023. Oral presentation.
Bernal Gomez A., Rivero-Buceta E., Vidaurre-Agut C., Vera-Donoso C.D., Moreno-Manzano V., Eric L., Benlloch J.M., Botella P. Towards a New Horizon in Prostate Cancer: PSMA-Targeted Docetaxel-Conjugated Nanomedicines for Intratumoral Treatment in Xenograft Model. European Association of Urology (EAU) 23. Milan (Italy) 10-13 March 2023. Poster presentation.
Irene Pi Martín, Carla María vidaurre Agut, Juan José García Garrigós, Alejandro Cebrecos Ruiz, Noé Jiménez González, Pablo Botella Asunción, Francisco Camarena Femenía. Imagen fotoacústica empleando nanopartículas de redes orgánicas covalentes (NCOFs) como agente de contraste. Tecniacústica 2023. Cuanca (España) 18-20 October 2023. Oral presentation.
A. González-Montoro et al., “MR compatibility assesment of the edgeless preclinical PET insert: ScintoTube,” 2023 IEEE Nuclear Science Symposium, Medical Imaging Conference and International Symposium on Room-Temperature Semiconductor Detectors (NSS MIC RTSD), Vancouver, BC, Canada, 2023. Poster presentation.
G. Cañizares, M. Freire, A. González-Montoro, H. Sabet, P. Bruyndonckx and A. J. Gonzalez, “Reducing edge effectsin semi-monolithicPET detectorsusing optical barriers: a simulation study,” 2023 IEEE Nuclear Science Symposium, Medical Imaging Conference and International Symposium on Room-Temperature Semiconductor Detectors (NSS MIC RTSD), Vancouver, BC, Canada, 2023. Poster presentation.