Enhanced drug retention in VX2 tumors by use of degradable starch microspheres.

Twenty-nine rabbits with 12- to 14-day-old VX2 tumors in the hind leg were injected intraarterially with technetium-99m (99mTc) DTPA and various combinations of biodegradable starch microspheres, Spherex (Pharmacia, Sweden), to evaluate the efficacy of the microspheres in enhancing tumor retention of 99mTc DTPA. A gamma camera and nuclear medicine computer were used to generate time activity curves of 99mTc DTPA concentration in the tumors. Blood flow to the tumor and various muscles was also measured at intervals by left ventricular injection of 15 micron radiolabeled plastic microspheres. Ninety minutes following the administration of 99mTc DTPA, specimens from the tumor, plasma and different muscles were counted in a NaI well counter connected to a multichannel analyzer. When biodegradable microspheres mixed with 99mTc DTPA were injected and followed by a slow infusion of plain starch microspheres, the 99mTc DTPA was retained in the tumor at concentrations up to 11 times that seen when 99mTc DTPA alone was injected; the corresponding biological half-time was 13 times longer than control values. Additionally, the degree of drug retention was inversely related to blood flow, with retention increasing as blood flow decreased. The results have possible applications to the use of biodegradable microspheres in the intraarterial delivery of chemotherapeutic agents to solid tumors.