Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery.
OBJECTIVE
The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR imaging. They also have found that this tracking technique allows monitoring of the distribution of similar nanosized agents such as therapeutic liposomes and viral vectors. A limitation of this procedure is the unexpected leakage of liposomes out of targeted parenchyma or malignancies into sulci and ventricles. The aim of the present study was to evaluate the efficacy of CED after the onset of these types of leakage.


METHODS
The authors documented this phenomenon in a study of 5 nonhuman primates and 7 canines, comprising 54 CED infusion sessions. Approximately 20% of these infusions resulted in leakage into cerebral ventricles or sulci. All of the infusions and leakage events were monitored with real-time MR imaging. The authors created volume-distributed versus volume-infused graphs for each infusion session. These graphs revealed the rate of distribution of GDL over the course of each infusion and allowed the authors to evaluate the progress of CED before and after leakage.


RESULTS
The distribution of therapeutics within the target structure ceased to increase or resulted in significant attenuation after the onset of leakage.


CONCLUSIONS
An analysis of the cases in this study revealed that leakage undermines the efficacy of CED. These findings reiterate the importance of real-time MR imaging visualization during CED to ensure an accurate, robust distribution of therapeutic agents.
Varenika
Vanja
V
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Dickinson
Peter
P
Bringas
John
J
LeCouteur
Richard
R
Higgins
Robert
R
Park
John
J
Fiandaca
Massimo
M
Berger
Mitchel
M
Sampson
John
J
Bankiewicz
Krystof
K
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018481:Convection; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics
D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium