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

Abstract

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 Tc-labeling of RBCs. However, these methods are complicated and lack reproducibility. Therefore, it is highly desirable to develop an alternative method for routineTc-labeling of RBCs. In this report, we present a novel approach for Tc-labeling of RBCs. We prepared a newTc(III) radiotracer [TcCl(CDO)(CDOH)B-4AS] (Tc-4ASboroxime: 4AS-B(OH) = 4-aminosulfonylphenyl)boronic acid, and CDOH = 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 Tc-4ASboroxime with low uptake in the myocardium, kidneys, liver, lungs, and muscle, most likely due to lack of leakage ofTc-labeled RBCs from the intravascular space. The blood radioactivity was almost unchanged over the 2 h period, suggesting that the binding of Tc-4ASboroxime to blood components (cells, proteins, and plasma) is stable. The results from γ-counting of the isolated blood components showed thatTc-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 Tc-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.Tc-4ASboroxime is an excellent blood pool agent with the potential for diagnosis and prognosis of vascular diseases.

Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens In Vivo Using Positron Emission Tomography

“…However, it seems unlikely that extrapulmonary manifestations of [ 64 Cu]­Cu-GRIP B uptake are merely due to red blood cell labeling as the temporin L/membrane interaction is potent and unlikely to dissociate in peripheral tissues. Qualitatively, [ 64 Cu]­Cu-GRIP B PET does not appear to demarcate the blood pool with the same effectiveness as radiolabeled red blood cells. , The source of the persistent liver signal is not clear to us. Genetic deletion of granzyme B significantly reduced the liver uptake of the radiotracer compared to infected wild-type mice, confirming that some of the liver accumulation requires granzyme proteolysis.…”

“…Qualitatively, [ 64 Cu]Cu-GRIP B PET does not appear to demarcate the blood pool with the same effectiveness as radiolabeled red blood cells. 51,52 The source of the persistent liver signal is not clear to us. Genetic deletion of granzyme B significantly reduced the liver uptake of the radiotracer compared to infected wild-type mice, confirming that some of the liver accumulation requires granzyme proteolysis.…”

68Ga-Labeled Maleimide for Blood Pool and Lymph PET Imaging through Covalent Bonding to Serum Albumin In Vivo

“…A variety of blood pool imaging agents labeled with radionuclides have been developed, most of which are based on red blood cells (RBCs) − or plasma albumin. , Currently, 99m Tc-labeled RBCs and human serum albumin ([ 99m Tc]­Tc-RBCs and [ 99m Tc]­Tc-HSA) are still used as two major agents for clinical blood pool imaging. Thinking of the low in vivo labeling efficiency, RBCs need to draw blood for in vitro labeling, which is a time-consuming process with the risk of potentially infectious substances .…”

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose

“…Experimentally, blood pool imaging is usually regarded as magnetic resonance vessel imaging. [37][38][39] However, blood pool imaging is almost always performed by hand bolus injection, with which the injection rate is limited, allowing the imaging time to be extended far beyond the short arterial first-pass phase. Therefore, most blood pool images are mixed images of the arterial and venous phases, which is different from clinical MR angiography and cannot be used for further clinical applications.…”