Use of Sonographic Contrast-enhanced Agents as an Alternative to Damaged Red Blood Cells for Imaging in Scintigraphy

Scintigraphy imaging is based on the uptake of radiopharmaceuticals by a tissue or organ. Hepatosplenic scintigraphy involves the uptake of labelled colloid by the mononuclear phagocyte system. The radiocolloid distribution in the body, where 80–90% is taken up by the liver, 5–10% by the spleen and 5% by the bone marrow, has the disadvantage of obscuring the rim of the spleen in patients with liver hypertrophy. However, the spleen takes up proportionally more particles if they are larger. While only 10–15% of 99mTc-sulfur colloid particles of 0.4 µ diameter are taken up by the spleen, about 90% of denatured red blood cells (RBCs), approximately 7 µm in diameter, are trapped in the splenic tissue. Because of this, labelled denatured RBCs are used for selective spleen imaging. RBCs present many disadvantages that preclude their use in clinical practice, as the steps involved in efficient labelling and denaturation of RBCs are labor-intensive, time-consuming, and not widely available. Therefore, an alternative method to denatured RBCs is highly desirable. Microbubbles, ultrasound-enhanced agents, are promising candidates for use as an alternative to damaged RBCs. Labelling of microbubbles is potentially simpler, safer, and less expensive. Furthermore, denatured RBCs and ultrasound contrast agents share certain characteristics, such as their size, shape, membrane composition and pharmacokinetics. Based on these similarities, the latter should be tested as an alternative carrier in scintillation scanning. Aside from the potential application of labelled microbubbles as a carrier alternative to denatured RBCs, they could also be used instead of natural RBCs for applications including the investigation of gastrointestinal bleeding, cardiovascular imaging studies, and to localize hemangiomas. Finally, they could be used in renal transplant recipients as a marker of rejection and as an adjunct to the diagnosis in certain diseases in which the immune response includes phagocytic cells.