Stable labeled microspheres to measure perfusion: validation of a neutron activation assay technique

Neutron activation is an accurate analytic method in which trace quantities of isotopes of interest in a sample are activated and the emitted radiatio n is measured with high-resolution detection equipment. This study demonstr ates the application of neutron activation for the measurement of myocardia l perfusion using stable isotopically labeled microspheres. Stable labeled and standard radiolabeled microspheres (15 mum) were coinjected in an in vi vo rabbit model of myocardial ischemia and reperfusion. Radiolabeled micros pheres were detected with a standard gamma-well counter, and stable labeled microspheres were detected with a high-resolution Ge detection after neutr on activation of the myocardial and reference blood samples. Regional myoca rdial blood flow was calculated from the deposition of radiolabeled and sta ble labeled microspheres. Both sets of microspheres gave similar measuremen ts of regional myocardial blood flow over a wide range of flow with a high linear correlation (r = 0.95-0.99). Neutron activation is capable of detect ing a single microsphere in an intact myocardial sample while providing sim ultaneous quantitative measurements of multiple isotope labels. This high s ensitivity and capability for measuring perfusion in intact tissue are adva ntages over other techniques, such as optical detection of microspheres. Ne utron activation also can provide an effective method for reducing the prod uction of low-level radioactive waste generated from biomedical research. F urther applications of neutron activation offer the potential for measuring other stable labeled compounds, such as fatty acids and growth factors, in conjunction with microsphere measured flow, providing the capability for s imultaneous measurement of regional metabolism and perfusion.