Radioactive Albumin Microspheres for Studies of the Pulmonary Circulation

Since its introduction into clinical medicine in 1963 (12), lung scanning has become a widely used method for determining the distribution of pulmonary arterial blood flow (13). The most common radiopharmaceutical for this purpose is 131 -labeled macroaggregates of human serum albumin (MAA), but more recently both 113mIn-labeled floes of iron hydroxide (10) and 99mTc-labeled MAA (4) have also been used. Attempts to extend the labeled particle distribution method to the study of the systemic circulation and to the measurement of arteriovenous shunting have failed because these particles are too irregular in size and too fragile (5). Such studies have been carried out in experimental animals with labeled ceramic or carbonized microspheres (2, 5, 7–9, 11). Although these microspheres have been used in man for in situ radiation therapy (1, 14), they have not been employed in diagnostic studies because they are not metabolized. To extend the methods which employ radioactive microspheres to the study of the human circulation, we have developed metabolizable, nontoxic microspheres which could be labeled with a variety of radionuclides (15). The purpose of this report is to describe radioactive albumin microspheres—a radiopharmaceutical useful for lung scanning and for measurements of arteriovenous shunting. Materials and Methods Microspheres: The microspheres were prepared by spheridizing a 25 per cent solution of human serum albumin in vegetable oil. Solidification of the microspheres was achieved by heating the oil suspension so that the temperature reached 130° C in forty-five minutes, then was maintained at this level for another thirty minutes. After this the microspheres were separated from the oil by filtration and washed with heptane and acetone or with diethyl ether to remove residual oil. For most of the studies we used microspheres made from albumin solutions containing a 10 per cent suspension of iron hydroxide which facilitated subsequent labeling with either 113mIn or 99mTc.2 Other microspheres were prepared by incorporating materials such as 59Fe(OH)3, Agl, AgCr04 or other precipitates in the initial albumin suspension. Microspheres were also made from 125I-labeled serum albumin. More detailed procedures for preparing microspheres will be reported elsewhere (15). For certain studies the microspheres were sieved to give particles of specific size ranges. All the microspheres used in human subjects had a mean diameter of 37.4 microns and a standard deviation of 8.2 microns. One milligram of these microspheres contained approximately 3 × 104 particles. More recently, microspheres in the size ranges 7–15, 5–25, 1525, 25–30, 30–45, 45–65 microns have been obtained.