²¹¹At-Radiolabeling Service

²¹¹At-labeling by covalent bonding of the powerful and short-range alpha-emitter astatine-211 to targeting vectors such as antibodies and peptides creates the exceptionally potent targeted alpha therapies. Alfa Cytology has the custom ²¹¹At conjugation capabilities and the required radiohalogen chemistry expertise, which allows them to develop the advanced radiopharmaceuticals required for the sophisticated preclinical studies.

Introduction to ²¹¹At Isotopes

Astatine-211 (²¹¹At) is extremely promising for targeted alpha therapy (TAT) due to its potent alpha-emitting radionuclide characteristics. Its half-life is 7.2 hours, during decays and emits a single high-energy alpha particle, which delivers a precise and deadly dose of radiation to cancer cells without damaging surrounding tissue. As a halogen, its exclusive chemistry permits stable, covalent labeling of peptides and antibody fragments, increasing its potential as a therapeutic agent.

Overview of ²¹¹At-Labeling for Radiopharmaceuticals

Astatine-211 (²¹¹At) labeling is essential to create highly effective alpha-emitting therapeutics. This radionuclide is ideal for targeting vectors that have intermediate pharmacokinetics, such as peptides and antibody fragments, due to the 7.2-hour half-life. Each decay produces one high-energy alpha particle, which is capable of cytotoxic and localized effects to the tumor. Unlike metal-based radiopharmaceuticals, the chemistry of ²¹¹At, being a halogen, enables stable and covalent conjugation.

Fig.1 Main reaction pathways for ²¹¹At radiolabeling. (GAO J, et al., 2024)

²¹¹At Radiopharmaceutical

Disclaimer: Alfa Cytology focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Alfa Cytology employs unparalleled knowledge and high-containment facilities to offer solutions for meticulously engineered and custom-label alpha particle therapeutics, focusing on overcoming the astatine-211 chemistry challenges. Partner with us to unlock the full potential of your novel biologics and move forward with confidence as you accelerate your high-impact therapeutic program from its conceptual stage to the preclinical validation stage.

Custom ²¹¹At Conjugation Service

²¹¹At conjugation enables the creation of potent, next-generation alpha-particle therapies by using advanced radiohalogenation methods to covalently attach the radionuclide, astatine-211, to novel targeting molecules.

Small-Molecule Radionuclide Conjugate (SMRC)

Antibody-Radionuclide Conjugate (ARC)

Peptide-Radionuclide Conjugate (PRC)

siRNA-Radionuclide Conjugate

Workflow for Developing ²¹¹At-Radiolabeled Antibody Conjugates

²¹¹At Custom Antibody Labeling

• Strategy & Reagent Selection: The important part of any successful radiolabeling project is a collaborative, scientifically rigorous design phase. This involves choosing a suitable astatine-binding moiety and designing a bifunctional linker. We optimize the conjugation chemistry, attributing high immunogenicity to the labeled conjugates while achieving favorable and stable final radiolabeled products.
• Precursor Synthesis: A bioconjugation process is used to quantitatively functionalize the naked antibody to attach the specific linker or prosthetic group required for the labeling method chosen. This step is carried out under tight conditions to avoid aggregation and non-specific modifications of the antibody.
• Custom Radiosynthesis: For maximum incorporation of ²¹¹At into the antibody conjugate while maintaining structural integrity, the incorporation reaction is performed under strictly controlled conditions of temperature, pH, and time. This is done in a specialized lab environment where advanced remote handling and shielding techniques are implemented to ensure maximum safety and efficiency.

Purification & Quality Control

Following the incorporation of ²¹¹At within the compound, the compound is thoroughly analyzed. To confirm the isotopic correct labeling, purity, and stability of the compound, and ensure the compound meets the required standards for biological studies, which is assessed by the various analytical measures of liquid chromatography (LC), mass spectrometry (MS), and scintillation counting.

• Stability Study Services
  To verify the stability of the final conjugate, we perform thorough stability studies, such as incubating the product in human or mouse serum at 37°C to evaluate serum in vitro stability. We obtain critical information on the conjugate's physiologically relevant stability profile by analyzing the samples over time using iTLC and HPLC for degradation of the conjugate's antibodies.
• Radiochemical Purity Evaluation Services
  Radiochemical Purity (RCP) is determined using different analytical techniques to verify product quality. iTLC gives a quick evaluation of the labeling efficiency. Analytical radio-HPLC or Size-Exclusion Chromatography (SEC) conclusively separates the intact radiolabeled antibody from its impurities, thus ensuring accurate and dependable purity assessment before a batch is released.
• Other Services
  Additional crucial evaluations expanded our quality control suite. We provide lipophilicity study services to calculate the log P value of the radiolabeled conjugate, which offers a preliminary understanding of the in vivo pharmacokinetics. Also, our immunoreactivity assay services are pivotal in demonstrating that the radiolabeling procedure does not significantly compromise the biological activity of the antibody.

In Vitro Evaluation

In vitro tests are performed to evaluate the biological properties of the ²¹¹At-labeled radiopharmaceutical. This includes studying its interaction with target receptors, cellular uptake, metabolic stability, and other pharmacological properties.

In Vivo Evaluation

The last part entails in vivo testing for the pharmacokinetics, biodistribution, and overall behavior of the radiolabeled compound. Using imaging and radiometric analysis, we gauge the tissue distribution of the ²¹¹At-labeled compound, yielding information on its possible therapeutic potential, safety, and tissue-specific targeting.

Applications of ²¹¹At-Radiolabeling

Harnessing the power of a single, highly cytotoxic alpha particle per decay, the applications of ²¹¹At-radiolabeling are focused on developing precision therapeutics designed to eradicate targeted cells with minimal collateral damage.

By working extensively with the complex radiohalogen chemistry of astatine-211 in our high-containment facilities, we have excellent capability in the development of well-defined and stably labeled alpha-particle therapeutics. To discuss the specifics of how we can tailor to your program, please reach out to us, and our specialists will ensure you receive the validated, preclinical-ready agent that meets your requirements.

Reference

1. GAO J, LI M, YIN J, et al. The Different Strategies for the Radiolabeling of [(²¹¹)At]-Astatinated Radiopharmaceuticals [J]. Pharmaceutics, 2024, 16(6).

For research use only. Not intended for any clinical use.