Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.
OBJECTIVE
To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging.


METHODS
One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically.


RESULTS
MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05).


CONCLUSIONS
Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.
Schwickert
H C
HC
Department of Radiology, University of California, San Francisco 94143, USA.
Stiskal
M
M
Roberts
T P
TP
van Dijke
C F
CF
Mann
J
J
Mühler
A
A
Shames
D M
DM
Demsar
F
F
Disston
A
A
Brasch
R C
RC
D000418:Albumins; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000528:radiation effects*; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003287:Contrast Media; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005682:Gadolinium; D019786:Gadolinium DTPA; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000532:radiotherapy*; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D051381:Rats; D011916:Rats, Inbred F344
D000418:Albumins; D000970:Antineoplastic Agents; D003287:Contrast Media; D046911:Macromolecular Substances; D009942:Organometallic Compounds; C058946:albumin-(gadolinium-DTPA); D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA; D002945:Cisplatin