Table 1.
Studies linking FUS-mediated blood-brain barrier opening to immunotherapy.
| Reference | Model | Ultrasound Parameters | Key Observations |
|---|---|---|---|
| 19 | Mouse (swiss webster) | Frequency: 0.69 MHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 40 sec Acoustic Pressure:0.6 - 1.1 MPa Microbubble type: Optison |
Delivery of D4 receptor antibody to mouse brain. No or minimal damage at 0.8 MPa or below. Major damage seen in some animals above 0.8 MPa. |
| 20 | Mouse (swiss webster) | Frequency: 0.69 MHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 40 s Acoustic Pressure: 0.6 and 0.8 MPa Microbubble type: Optison |
Delivery of Herceptin. Significantly greater amount delivered at 0.8 MPa than 0.6 MPa |
| 36 | Rabbit (New Zealand white) | Frequency: 1.63 and 1.5 MHz Burst length: 100 ms Repetition frequency: 1 Hz Exposure length: 20 s Acoustic Power: 0.55 or 3 W Microbubble type: Optison |
Sonication as 0.55 W resulted in increased vescicles and vacuoles in endothelial cells, fenestrae on EC luminal surface, and widened inter-endothelial cleft, and IgG was detected. Significant damage was seen at 3W. |
| 37 | Transgenic mice (B6C3-Tg and PDAPP) | Frequency: 0.69 MHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 40-45 s Acoustic Pressure: 0.67-0.8 MPa Estimated acoustic power: 0.28-0.4 W Microbubble type: Optison or Definity |
Delivery of anti-Amyloid β antibodies in two different transgenic AD mouse models yielded a roughly 3-fold increase in antibody localized to plaques |
| 38 | TgCRND8 mice | Frequency: 0.558 MHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 120 s Acoustic Pressure: 0.3 MPa Microbubble type: Definity |
Delivery of amyloid-β antibodies that colocalize with plaques on US treated hemisphere. In mice treated with FUS + anti-amyloid antibody, there was a 12% reduction in plaque number and 23% reduction of plaque size in the FUS treated hemisphere |
| 39 | non-Tg and TgCRND8 mice | Frequency: 0.5 MHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 120 s Acoustic Pressure: 0.3 MPa Microbubble type: Definity |
FUS-mediated BBB opening alone facilitates binding of endogenous antibodies to amyloid beta plaques, yielding reduced plaque load and activation of microglia |
| 40 | pR5 mice | Frequency: 1 MHz Burst length: 10 ms Repetition frequency: 10 Hz Exposure length: 6 s per spot Acoustic Pressure: 0.7 MPa Microbubble type: In-house, lipid-shelled |
The entire forebrain of the mouse was sonicated by sequential 6 s sonications per spot. Administration of RN2N with microbubbles and scanning ultrasound yielded an 11-fold increase in RN2N delivery, a reduction of anxiety-like behavior, and tau phosphorylation compared to groups given RN2N was administered without ultrasound. |
| 41 | Nude rats (intracranial MDA-MB-361 cells) | Frequency: 690 kHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 60 s Acoustic Pressure: 0.46-0.62 MPa Acoustic Power: 0.4-0.7 W Microbubble type: Optison |
A subset of animals in the FUS + antibody (trastuzimab and pertuzumab) showed slower tumor growth rate (responsders), while there were no responders in the antibody only group. There was increased survival in the FUS + antibody and antibody only groups compared to untreated animals, but no statistically significant difference between these two groups. |
| 42 | Nu/Nu mice (intracranial U87mg cells) | Frequency: 400 kHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 60 s Acoustic Pressure: 0.4-0.8 MPa Acoustic power = 4-18 W Microbubble type: Sonovue |
Weekly treatments with FUS, microbubbles, and bevacizumab resulted in decreased tumor growth, increased median overall survival, and decreased vessel area compared to untreated, FUS only, and bevacizumab only groups |
| 44 | Sprague-Dawley rats (intracranial C6 glioma) | Frequency: 0.5 MHz Burst length: 100 ms Repetition frequency: 1 Hz Exposure length: 90 s Acoustic Pressure: 0.36-0.7 MPa Acoustic Power: 5 or 20 W Microbubble type: Sonovue |
I.P. administration of IL-12 followed by application of FUS and microbubbles resulted in an approximately three-fold increase in IL-12 compared to untreated control mice. Mice receiving IL-12 with FUS had the highest CD8+/T-reg ratio, slowed tumor progression, and the greatest survival benefit |
| 45 | Athymic nude rat (intracranial MDA-MB-231 cells) | Frequency: 551.5 kHz Burst length: 10 ms Repetition frequency: 1 Hz Exposure length: 120 s Acoustic Pressure: 0.32-0.35 MPa Microbubble type: Definity |
FUS administration generated a 10-fold increase in HER2-specific NK-92 cells abundance in the FUS-targeted region after i.v. NK-92 injection when compared to i.v. NK-92 injection without FUS |
| 46 | Athymic nude rat (intracranial MDA-MB-231 cells) | Frequency: 551.5 kHz Burst length: 10 ms Repetition frequency: 2 Hz Exposure length: 120 s Acoustic Power: Used a controller to monitor acoustic emissions and modulate acoustic power to predetermined ultraharmonic signatures. Microbubble type: Definity |
With aggressive treatment schedule, animals in the FUS + NK-92 group showed a reduction in tumor growth and increase in survival compared to controls |