Delivering Gd-Labeled IgG Antibodies Into the Mouse Brain Following Focused Ultrasound Treatment.

Antibody-based therapy has emerged as a powerful tool for targeted treatment of neurological diseases, such as brain cancer and neurodegenerative disorders. However, direct, scalable, and safe confirmation of antibody delivery into the brain remains challenging. Antibodies can be effectively tracked when tagged with molecules that are detectable by medical imaging modalities, such as MRI, PET, or SPECT. In this study, we aimed to confirm gadolinium (Gd)-labeled IgG antibody delivery into the mouse brain using MRI, following exposure to focused ultrasound (FUS) and circulating microbubbles. We acquired MR images of the mouse brain to evaluate antibody delivery into the targeted brain region. First, we quantified the MR signal of Gd-labeled IgG antibodies in phantoms using preclinical 9.4 T and clinical 3 T MRI scanners. Then, we determined optimal ultrasound and MR imaging parameters to non-invasively and safely disrupt the blood-brain barrier in a localized and reversible manner and effectively monitor antibody delivery into the murine brain, respectively. We confirmed that IgG antibodies can be reliably delivered into the murine brain using FUS and microbubble treatment and that we can track their biodistribution within the brain parenchyma using clinically relevant MR image sequences. The maximum detected volume of Gd-IgG antibody delivery (n = 4) was determined to be 0.12 ± 0.02 mm³ at t = 75.3 ± 17.3 minutes following treatment. This work paves the way for a scalable and non-ionizing method for performing and evaluating antibody delivery into the brain.