Fig. 5.

Physiological barriers that a blood-borne molecule encounters before it reaches a cancer cell in a solid tumor. (a) Schematic of a heterogeneously perfused tumor showing well-vascularized periphery; a seminecrotic, intermediate zone; and an avascular, necrotic central region. Note that, immediately after i.v. injection, the molecules are delivered to perfused regions only. (b) Low interstitial pressure in the periphery permits adequate extravasation of fluid and macromolecules. (c) These macromolecules move toward the center by the slow process of diffusion. In addition, interstitial fluid oozing from tumor carries macromolecules with it by convection into the normal tissue. Note that the interstitial movement may be further retarded by binding. Products of metabolism may be cleared rapidly by blood (reproduced from Ref. [102]).