Retention and biodistribution of microspheres injected into ischemic myocardium

Abstract

Intramyocardial injection of therapeutic agents may enhance heart repair after infarction. Incomplete retention of intramyocardial injections has been reported, but modes of loss are undefined. We determined the fate of neutron-activated microspheres injected into acutely ischemic rat myocardium using saline, Pluronic F127, or Matrigel as vehicle. Twenty minutes after injection in saline, 63% +/- 12% of 10-mum microspheres was retained in the heart. Similar retention was observed after 6 days. Injection site leakage accounted for 14% +/- 5% of the microspheres, whereas exit via coronary veins resulted in 11.2% +/- 9.5% collecting in the lungs. Microspheres distribution to other organs was minimal. Retention of 40-mum microspheres was similar to that observed with the 10-mum microspheres. Pluronic F127 and Matrigel reduced immediate leakage to 4% +/- 1% and 2% +/- 1%, respectively. Surprisingly, microsphere retention in the heart was not improved at 20 min using either gelling vehicle, suggesting that leakage occurs over a prolonged period. Thus, most injected particles are retained in the ischemic rat heart following direct injection, but significant fractions are lost from the injection site and through coronary veins. Gelling agents reduced short-term leakage, but failed to enhance longer-term retention. Hydrogels with stiffer mechanical properties might enhance retention and reduce variability.