High-resolution magnetic resonance imaging of disparities in the transcapillary transfer rates in orthotopically inoculated invasive breast tumors.
In vivo mapping of the transcapillary fluxes in tumors can help predict the efficacy of delivery of blood-borne anticancer drugs. These fluxes are primarily affected by the vascular permeability and the pressure gradients across the blood vessels' walls. We describe herein high-resolution dynamic contrast-enhanced magnetic resonance imaging of the influx and outflux transcapillary transfer rates in vivo in invasive MDA-MB-231 tumors orthotopically inoculated in severe combined immunodeficient mice. The tumors were noted for rapid growth, impaired drainage of fluid, and subsequent formation of cysts. Consequently, the time evolution of the contrast enhancement, induced by i.v. injection of Gadolinium diethylene-triamine-penta-acetate, exhibited two distinct patterns: transcapillary transfer in the cellular regions and simple diffusion in the cyst fluid. Both processes were analyzed at pixel resolution applying to each a physiological model and a corresponding algorithm. In the cellular region, the influx and outflux transcapillary transfer rates decreased during tumor growth; however, an increased disparity between the transfer constants was observed, with the outflux rate exceeding the influx rate. This quantitative spatial and temporal mapping of this disparity can provide a means to assess the physiological barriers to tracer delivery. It is hypothesized that both the increased disparity in transcapillary transfer rates and impaired fluid drainage in these tumors could arise from the development of interstitial hypertension.
Dadiani
Maya
M
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Margalit
Raanan
R
Sela
Noa
N
Degani
Hadassa
H
D000818:Animals; D001943:Breast Neoplasms / Q000097:blood / Q000098:blood supply* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D018810:Magnetic Resonance Angiography; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation
D003287:Contrast Media; D019786:Gadolinium DTPA