Monitoring blood-brain barrier status in a rat model of glioma receiving therapy: dual injection of low-molecular-weight and macromolecular MR contrast media.
OBJECTIVE
To evaluate the sequential injection of a low-molecular-weight (gadoterate meglumine [Gd-DOTA], 0.5 kDa) and a macromolecular (P846, 3.5 kDa) contrast media in monitoring the effect of antitumor therapies (antiangiogenic therapy and/or microbeam radiation therapy [MRT]) on healthy brain tissue and implanted tumors.


METHODS
Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Eighty male rats bearing 9L gliosarcoma were randomized into four groups: untreated, antiangiogenic (sorafenib) therapy, MRT, and both treatments. Magnetic resonance (MR) imaging was performed 1 day before and 1, 5, and 8 days after the start of the treatment. At all time points, vascular integrity to a macromolecular contrast medium (P846) and, 11 minutes 30 seconds later, to low-molecular-weight contrast medium (Gd-DOTA) was evaluated by using a dynamic contrast material-enhanced MR imaging approach. To quantify vessel wall integrity, areas under the signal intensity curves were computed for each contrast medium. Unpaired t tests and one-way analysis of variance were used for statistical analyses.


RESULTS
Tumor vessels receiving antiangiogenic therapy became less permeable to the macromolecular contrast medium, but their permeability to the low-molecular-weight contrast medium remained unchanged. Healthy double-irradiated vessels became permeable to the low-molecular-weight contrast medium but not to the macromolecular contrast medium.


CONCLUSIONS
Antiangiogenic therapy and MRT generate different effects on the extravasation of contrast medium in tumoral and healthy tissues. This study indicates that the use of a low-molecular-weight contrast medium and a macromolecular contrast medium provides complementary information and suggests that the use of two contrast media within the same MR imaging session is feasible.
Lemasson
Benjamin
B
INSERM U836, Grenoble, France.
Serduc
Raphaël
R
Maisin
Cécile
C
Bouchet
Audrey
A
Coquery
Nicolas
N
Robert
Philippe
P
Le Duc
Géraldine
G
Troprès
Irène
I
Rémy
Chantal
C
Barbier
Emmanuel L
EL
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001557:Benzenesulfonates / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000532:radiotherapy; D009536:Niacinamide / Q000031:analogs & derivatives; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D000077157:Sorafenib
D001557:Benzenesulfonates; D003287:Contrast Media; D006571:Heterocyclic Compounds; D046911:Macromolecular Substances; D009942:Organometallic Compounds; C531154:P846 compound; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D000077157:Sorafenib