Characterization of patient-derived site-specific in vivo models of pediatric-type diffuse high-grade glioma using magnetic resonance imaging
Por:
Boult, Jessica K. R., Carvalho, Diana M., Kessler, Ketty, Molinari, Valeria, Mackay, Alan, Grabovska, Yura, Fofana, Mariama, Taylor, Kathryn R., Bjerke, Lynn, Fernandez, Elisabet, Pereira, Rita, Clarke, Matthew, Temelso, Sara, Burford, Anna, Sejdiu, Drenusha, Carcaboso AM, Cockle, Julia, V, Carceller, Fernando, Marshall, Lynley, V, Vaidya, Sucheta J., Bridges, Leslie R., Singh, Navneet, Stapleton, Simon, Hettige, Samantha, Al-Sarraj, Safa, Reisz, Zita, Zebian, Bassel, Bleil, Cristina, Grundy, Richard G., Gray, Juliet C., Hargrave, Darren, Wilson, Shaun, Picton, Susan, Adamski, Jenny K., Hassall, Timothy E. G., Mastronuzzi, Angela, Carai, Andrea, Benjamin, Philip, Colafati, G. Stefania, Vinci, Maria, Jones, Chris and Robinson, Simon P.
Publicada:
1 ene 2026
Ahead of Print:
27 feb 2026
Resumen:
Background There is an urgent need for novel targeted therapeutic strategies for pediatric-type diffuse high-grade glioma (PDHGG) to improve patient outcomes, the development of which demands model systems that accurately recapitulate the specific PDHGG subtypes. Characterization, longitudinal monitoring and, ultimately, evaluation of treatment response in these models requires sensitive non-invasive imaging techniques such as magnetic resonance imaging (MRI).Methods Thirty-five patient-derived, site-specific, orthotopic in vivo models of PDHGG, established using implantation of patient tumor material or patient-derived in vitro cultures maintained in stem cell retaining conditions, were characterized using multiparametric MRI.Results Median survival ranged from 54 to 433 days. Tumors identified on T2-weighted (T2w) images varied in appearance from a diffuse hyperintense signal to well-defined high contrast masses, and distribution of human nuclear antigen positive tumor cells corresponded to regions of T2w signal hyperintensity. Apparent diffusion coefficient was significantly higher in brainstem diffuse midline glioma (DMG) models than in diffuse hemispheric glioma (DHG) tumors, mirroring clinical observations. Lack of contrast-agent enhancement indicated an intact blood-brain barrier in most models, with heterogeneous disruption observed in four DHG models. Upon re-implantation, survival was significantly shortened in 3/4 DHG tumors and 1/10 DMG models, while quantitative MRI parameters remained similar. Furthermore, when 3 models grown in 2D and 3D in vitro were implanted in parallel, poorer survival or improved penetrance was associated with 3D cultures.Conclusion We established a comprehensive pre-clinical platform in which to evaluate the efficacy of therapeutic strategies against PDHGG in vivo, enhanced by the use of multiparametric MRI.
Green Submitted, gold
|