Intralesional and Intraparenchymal Convection-Enhanced Delivery of Nanoparticles

Convection-enhanced delivery (CED) is a technique that involves injecting therapeutics directly using catheters inserted through surgery, utilizing a hydrostatic pressure gradient to improve the distribution. Although the clinical trials conducted so far have yet to demonstrate the benefits of CED, the lack of success can be partly attributed to technical limitations and insufficient tumor coverage. These trials emphasize the need to verify the precise distribution of each injected substance, as the delivery can be unpredictable and may not reach the intended target. Real-time imaging with MRI traceable vectors can be employed to gain insight into the distribution and facilitate subsequent injections. While CED has shown promise in small animal xenograft models for initial proof-of-concept studies, validating these findings in larger animal models that more accurately resemble human tumors, especially for each specific vector system, is crucial. Canine gliomas that occur naturally was used as a model system for investigating image-guided therapy based on convection-enhanced delivery (CED). These studies conducted in dogs with spontaneous gliomas have the potential to drive progress in both human and canine oncology care. These naturally occurring tumors in dogs are diverse and sizable, making them well-suited for preclinical investigations of innovative treatments. Moreover, canine gliomas share numerous molecular characteristics with their human counterparts, enhancing their relevance as a research model. Stereotactic delivery of paramagnetic nanoparticles (PMNPs) was precisely performed at the center of the tumor. Post-operative MRI scans were conducted immediately to assess the distribution of PMNPs, and the animals were monitored until their demise. In 70% of the cases, the infusion accurately targeted the tumor mass, evidenced by a PMNP signal within the tumor on the immediate post-operative MRI scans. These findings indicate that the convection-enhanced delivery (CED) of PMNPs carrying TMZ is safe for dogs with intracranial tumors, resulting in nanoparticle distribution within the intended region. Image guidance is crucial as it assists in achieving optimal CED, considering the unpredictable nature of distribution and the potential risk of missing the target site. These principles will require formal clinical trials before routine application in clinical practice.