Radiolabeled Red Blood Cells: An Overview

Introduction

Red blood cells that contain technetium-99m, a crucial element in modern nuclear medicine, are the subject of this study. Even with the hazards and technological difficulties involved, the use of autologous blood products for imaging has remained the same since the publication's original 1992 release.

Although new materials have emerged in recent years, including derivatized human serum albumin products and radiolabeled synthetic graft copolymers, they have yet to produce a blood pool imaging product that is commercially available. High development costs and this medicine class's small commercial potential are likely obstacles.

The extensive application of Tc-99m red blood cells has raised awareness of potential hazards and uncovered interfering factors impacting their in vivo behavior, even if the basic techniques and mechanisms have remained the same.

What Are the Clinical Indications of Radiolabeled Red Blood Cells?

In medicine, radiolabeled red blood cells are used for several reasons, mostly in five areas:

• Determining Total Red Blood Cell Volume: Identifying the body's total red blood cell volume.

• Determining Red Blood Cell Survival Time: Calculating the blood's red blood cell survival duration.

• Identifying Red Blood Cell Destruction Sites: Identifying the locations where red blood cells deteriorate.

• Studies on Blood Pool Imaging: This includes specialized imaging such as the detection of gastrointestinal bleeding and gated cardiac imaging, which involves watching the heart's blood pool.

• Selective Spleen Imaging With Injured Red Blood Cells: This approach focuses on imaging the spleen with potentially injured red blood cells.

For each use, different characteristics of tagged red blood cells are required. Depending on the kind of investigation, variables such as the physical characteristics of the radionuclide, its stability in vivo, and its labeling ease all have distinct effects. For example, a radionuclide with a long physical half-life and strong stability in the body is needed to measure the red blood cell survival time. However, a radionuclide with a short half-life is required for cardiac blood pool imaging tests, which are frequently completed fast. As these studies are frequently carried out across numerous medical facilities, labeling speed and ease of use are crucial factors.

How Has Tc-99m Impacted the Use of Radioactive Substances for Labeling Red Blood Cells in Medicine?

Since George de Hevesy employed P-32 (Chromic phosphate P 32) to quantify blood volume for the first time in the 1940s, radioactive chemicals have been utilized to identify red blood cells for medical purposes. Subsequently, Sterling and Gray presented an improved technique with Cr-51 (Chromium 51), gaining popularity since it was so simple. However, because of its low gamma ray abundance, there are better choices for imaging than Cr-51. Despite this, it is nevertheless utilized for particular lab examinations.

Although they have certain limits, other radioactive isotopes such as Fe-55 (iron 55) and Fe-59 have been employed. Numerous techniques have been investigated, each with pros and cons, utilizing various isotopes, including C-14 (Carbon-14) and Hg-197 (mercury-197).

Rb-81 (Rubidium-81) has shown potential recently because of its short half-life and applicability in specific research. Furthermore, more advanced methods for imaging the spleen using isotopes like C-11 have been developed, although they need specific equipment.

Better choices for labeling platelets and white blood cells were made available with the advent of In-111 (Indium-111). It helps track procedures over a few days. However, because of its physical characteristics, its usage for red blood cells is restricted.

TC-99 m's (Technetium-99m) superior imaging qualities transformed the field. In nuclear cardiology, blood pool imaging is a frequent application that yields fine-grained images of dynamic processes. To guarantee good imaging, though, its binding to red blood cells must be carefully regulated.

What Are the Steps Involved in Labeling Rbcs With Tc-99m?

The three fundamental processes that are involved in the technetium labeling of red blood cells are:

• Red Blood Cell Treatment With Stannous Ions: Technetium is reduced by stannous ions, allowing it to attach to hemoglobin in red blood cells. For this, stannous chloride, typically soluble, is frequently utilized. It enters the bloodstream directly through injection. While the exact amount required varies, it usually ranges from 10 to 20 micrograms per kilogram of body weight.

• Eliminating Excess Stannous Ion: Reducing the level of stannous ions in the blood is necessary before proceeding to the next stage because it can lead to issues. This is often accomplished by waiting 20 to 30 minutes following stannous ion injection to allow the body to expel any excess. Some techniques involve accelerating this process with an oxidizing substance, such as sodium hypochlorite.

• Addition of Technetium Pertechnetate: The red blood cells are treated with technetium pertechnetate after the excess stannous ion has been eliminated. This enables the technetium to attach itself to the red blood cells that have already received treatment, designating them for imaging or other uses. This process might occur inside the body or externally in a lab environment.

What Are the Current Methods of Labeling Rbcs With Tc-99m?

Current techniques for Tc-99m labeling of red blood cells:

• In Vitro Kits: These kits provide an easier substitute for the more complex stannous chloride procedure. They employ materials such as stannous glucoheptonate or citrate. One benefit is that time can be saved by prepping these kits in advance. Certain kits, like Ultra-Tag, even employ sodium hypochlorite to eliminate surplus stannous ions, further simplifying and expediting the procedure.

• In Vivo Techniques: This technique injects Tc-99m pertechnetate after stannous pyrophosphate. It was found when patients with prior bone scans displayed anomalous distributions of Tc-99m pertechnetate in their brain scans. Although the labeling efficacy of this procedure varies, it is often easier to use than the in vitro method.

• Modified In Vivo Techniques: These techniques seek to raise the standard of pictures produced by in vivo labeling. One technique separates red blood cells and Tc-99m pertechnetate before labeling to achieve better binding. To ensure effectiveness, this approach needs certain circumstances and cautious timing.

While each approach has pros and cons, they are all intended to simplify and improve the technology of tagging red blood cells for medicinal applications.

What Is the Mechanism of Labeling?

It has been found that most radioactivity adheres to the hemoglobin when Tc-99m is used to identify red blood cells. Subsequent investigation revealed that around 90 percent of this activity is connected to the heme component of the hemoglobin molecule and the remaining 87 percent to the globin part. Researchers think Tc-99m, most likely in a lower valence state (technetium +4), creates a strong, difficult-to-reverse bind with globin, particularly the beta-chain.

Research has indicated that passive diffusion into the cell is the primary mechanism by which pertechnetate, a kind of technetium, binds to red blood cells. However, more recently, it has been discovered that a mechanism known as band-3 anion transport can also carry pertechnetate ions across the membrane of red blood cells. Normally, the amounts of bicarbonate and chloride within the cell are managed by this mechanism. Pertechnetate can readily exit the cell if suspended in a solution containing bicarbonate or chloride because it lacks an internal mechanism to reduce pertechnetate without requiring a reducing agent. On the other hand, pertechnetate can be reduced and subsequently bind to hemoglobin when a reducing agent—such as stannous ions—is present inside the cell.

What Are the Factors Affecting Labeling Efficiency?

According to studies, the body gradually incorporates Tc-99m into red blood cells over time, with 91.4 percent incorporation occurring 10 minutes after injection. This shows that Tc-99m not attached to red blood cells is significantly available for dispersion outside blood vessels, most likely pertechnetate.

• Temperature: Syringes should be kept at 37ºC (degree Celsius) throughout incubation to maximize labeling efficiency, as higher temperatures speed up the labeling process. Severe temperatures can cause enough damage to red blood cells to prevent selective spleen imaging, such as raising the syringe temperature to 49 to 50ºC.

• Hematocrit: The rate and degree of red blood cell labeling are strongly influenced by hematocrit levels. Age and sex-specific normal hematocrit ranges exist, but lower values in patients suffering from anemia or severe blood loss increase extravascular Tc-99m activity and decrease labeling efficiency. Modifying the incubation periods may help lessen this effect for patients with low hematocrit levels.

• Volume of Whole Blood: Labeling characteristics remain largely unaffected by increasing the volume of whole blood within a specific range.

• Effect of Plasma: The presence of plasma reduces the labeling efficacy of red blood cells, suggesting that the concentration of both plasma and red blood cells influences labeling efficiency.

Conclusion

A unique class of medication known as radiolabeled red blood cells is used to measure blood volume and circulation. Tc-99m is a label that is frequently used and is useful for measuring blood in the body and taking photographs. Blood cells can be labeled in various ways; one method simplifies the process by combining several techniques. Doctors can ensure that a medication is effective for testing by adhering to specific guidelines and using caution regarding the temperature and quantity of drugs employed. Although using one's blood for testing presents certain difficulties, it is nonetheless widely utilized because it is effective. Other methods are under investigation, but for financial and other reasons, they are not yet generally accessible. Thus, testing on an individual's blood will likely continue for the time being.