Novel Approach for 99mTc-Labeling of Red Blood Cells: Evaluation of 99mTc-4SAboroxime as a Blood Pool Imaging Agent.

Angiography with radiolabeled red blood cells (RBCs) plays an important role in diagnosis and prognosis in vascular diseases. Both in vitro and in vivo methods have been developed for 99mTc-labeling of RBCs. However, these methods are complicated and lack reproducibility. Therefore, it is highly desirable to develop an alternative method for routine 99mTc-labeling of RBCs. In this report, we present a novel approach for 99mTc-labeling of RBCs. We prepared a new 99mTc(III) radiotracer [99mTcCl(CDO)(CDOH)2B-4AS] (99mTc-4ASboroxime: 4AS-B(OH)2 = 4-aminosulfonylphenyl)boronic acid, and CDOH2 = cyclohexanedione dioxime) in >95% radiochemical purity. Imaging and biodistribution studies were performed in Sprague-Dawley (SD) rats. It was found that the blood radioactivity was ∼6.0%ID/g (∼90% injected dose for 200-225 g SD rats) for 99mTc-4ASboroxime with low uptake in the myocardium, kidneys, liver, lungs, and muscle, most likely due to lack of leakage of 99mTc-labeled RBCs from the intravascular space. The blood radioactivity was almost unchanged over the 2 h period, suggesting that the binding of 99mTc-4ASboroxime to blood components (cells, proteins, and plasma) is stable. The results from γ-counting of the isolated blood components showed that 99mTc-4ASboroxime had >95% of blood radioactivity binding to RBCs, ∼1% to albumin, and ∼3% remaining free in blood plasma, demonstrating its RBC-specificity. The results from imaging studies in SD rats indicated that 99mTc-4ASboroxime is predominantly distributed in the blood pool. Main blood vessels were well delineated in the head/neck and abdominal regions. This statement was further substantiated by the results from imaging studies in pigs. 99mTc-4ASboroxime is an excellent blood pool agent with the potential for diagnosis and prognosis of vascular diseases.