Revistas
Autores:
Puyalto, A.; Rodriguez-Remírez, M.; López, I.; et al.
Revista:
FRONTIERS IN IMMUNOLOGY
ISSN:
1664-3224
Año:
2023
Vol.:
14
Págs.:
1272570
Background: Harnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [89Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC.
Materials and methods: A syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [89Zr]-labeled anti-PD-1 antibody and measured as 89Zr tumor uptake.
Results: Conventional [18F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [89Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [89Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001).
Conclusion: Our data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC.
Revista:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1619-7070
Año:
2023
Vol.:
50
N°:
Supl. 1
Págs.:
S444
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:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1619-7070
Año:
2022
Vol.:
49
N°:
Supl. 1
Págs.:
S663
Revista:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN:
1619-7070
Año:
2022
Vol.:
49
N°:
Supl. 1
Págs.:
S446 - S447
Nacionales y Regionales
Título:
NANO-IMMUNOTHERAPY: INTRACELLULAR TARGETING OF CANCER CELLS AND TAMS
Código de expediente:
PCIN-2017-017
Financiador:
MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
Convocatoria:
2017 MINECO APCIN
Fecha de inicio:
01/10/2017
Fecha fin:
30/06/2021
Importe concedido:
100.000,00€
Otros fondos:
-
Título:
2^2-INTRATARGET: nanomedicinas para la liberación de administrar anticuerpos
Código de expediente:
AC20/00117
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2020 AES Programación Conjunta Internacional
Fecha de inicio:
01/01/2021
Fecha fin:
01/07/2024
Importe concedido:
174.998,67€
Otros fondos:
-
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
Otros (PIUNA, fundaciones, contratos…)
Título:
Targeted Radiotherapy using a peptide targeting
Investigador principal:
Alfonso Calvo González
Fecha de inicio:
26/07/2023
Fecha fin:
31/12/2024
Importe:
121.500,00€
Otros fondos:
-