¹¹¹In-Radiolabeling Service

¹¹¹In-radiolabeling service offers a bespoke conjugation service on biologics, unique and custom. We utilize the half-life of the isotope, which is 2.8 days, to produce exceptionally stable SPECT agents for multi-day imaging of antibodies and peptides. Alfa Cytology has an intimate understanding of the complex chelation chemistry of Indium-111 and has the capability to offer custom-labeled radiopharmaceuticals development services. This is extremely useful for further advanced preclinical studies.

Introduction to ¹¹¹In Isotopes

Indium-111 (¹¹¹In) is a cyclotron-produced radioisotope of indium that is important and which is extensively used in diagnostic nuclear medicine. Indium-111 has a physical half-life of around 2.8 days (67.2 hours), which is considered favorable for various diagnostic procedures. This also provides time for the radiopharmaceutical to localize and for other imaging procedures, and also minimizes the long-term radiation dose to the individual.

¹¹¹In-Labeling for Radiopharmaceuticals

Indium-111 (¹¹¹In) is a preferred radionuclide for use in radiopharmaceuticals, especially in single photon emission computed tomography (SPECT) imaging. Its use is due to its advantageous decay properties and diverse coordination chemistry. Labeling is done using bifunctional chelators, primarily diethylenetriaminepentaacetic acid (DTPA), or DOTA-type macrocyclic agents. The targeting molecules, such as peptides or antibodies, are first covalently modified to the chelators and then complexed to the trivalent ¹¹¹In³⁺ ion, thus enabling tracking of the physiological and pathological processes in the body.

Fig.1 Chemical structures of [¹¹¹In]In-PNT-DA1 (A) and [111In]In-PSMA-617 (B). (KAZUTA N, et al., 2024)

¹¹¹In 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.

Advantages of ¹¹¹In-Labeling

For the development of radiopharmaceuticals, the combination of unrivaled destructive power and microscale precision of the isotope ¹¹¹In is distinctive. Its remarkable therapeutic benefits originate from the isotope’s particular decay cascade, providing intense and precisely focused alpha-particle radiation to the targeted malignant cells.

The intermediate half-life of indium-111, coupled with stable gamma emissions and clear stable coordination chemistry, makes it a versatile and effective radionuclide for imaging diagnostics and tracing intricate biological phenomena.

Our Services

Combining knowledge gained during the years of radiochemistry with that of bioconjugation, Alfa Cytology provides custom Indium-111 labeling services for simple as well as complex biomolecules such as peptides, antibodies, and nanoparticles. Having years of experience, our team provides solutions for stable and highly purified radioconjugates to preclinical research as well as diagnostic imaging.

Small-Molecule Radionuclide Conjugate (SMRC)

Antibody-Radionuclide Conjugate (ARC)

Peptide-Radionuclide Conjugate (PRC)

siRNA-Radionuclide Conjugate

Radiolabeling Antibody with ¹¹¹In for SPECT Imaging

¹¹¹In Custom Antibody Labeling

Our dedicated service offers comprehensive solutions for the preparation of Indium-111 labeled antibodies, which are important for preclinical research SPECT imaging with high sensitivity and specificity. We guarantee reagents with the desired specific activity, immunoreactivity, and in vivo stability.

• Strategy & Reagent Selection: Our specialists collaborate with you to establish fundamental parameters, such as target epitope, antibody isotype, and application. From there, we choose the best bifunctional chelator (e.g., DOTA), establish the specific activity required, and create a conjugation approach that preserves the most critical antigen-binding features of your antibody.
• Antibody Conjugation: Under optimal conditions, your antibody gets linked with a selected chelator. After, the conjugate undergoes purification by size-exclusion chromatography or dialysis for the removal of unreacted chelator, resulting in a purified intermediate ready for radiolabeling.
• Protocol Optimization: The purified conjugate is reacted with ¹¹¹In-chloride in a controlled buffer system. To obtain a stable ¹¹¹In-antibody complex with maximum radiochemical yield, we optimize key variables systematically, such as pH, temperature, and incubation duration.
• Custom Radiosynthesis: To ensure safety and consistency, radiolabeling takes place in a controlled setting, typically inside a shielded hot cell with an automated synthesizer module. The process involves the conjugated antibody and ¹¹¹In, precise mixing, the optimal conditions for incubation, followed by termination.

Purification & Quality Control

Verification comes after labeling to confirm successful incorporation of ¹¹¹In. Liquid chromatography (LC), mass spectrometry (MS), and scintillation counting are analytical methods employed to ascertain effective isotopic labeling, purity, and the overall stability of the compound while also undertaking assurance of the compound up to the standards required for its biological applications.

In Vitro Evaluation

In vitro tests are performed to evaluate the biological properties of the ¹¹¹In-labeled radiopharmaceutical. This includes studying its interaction with target receptors, cellular uptake, metabolic stability, and other pharmacological properties.

In Vivo Evaluation

This critical phase begins with quantitative biodistribution and pharmacokinetic (PK) studies that measure the agent's retention in different tissues and the rates at which it is eliminated from the body. Then, in designated disease models, SPECT imaging is undertaken to confirm target engagement visually and to perform in vivo blocking experiments to conclusively verify the agent's diagnostic utility.

Applications of ¹¹¹In-Radiolabeling

Characterized by its long 2.8-day half-life, the applications of ¹¹¹In-radiolabeling are centered on providing high-quality, multi-day SPECT imaging. This enables ¹¹¹In-radiolabeling to in vivo track the biodistribution and pharmacokinetics of multispecific monoclonal antibodies as well as other slow-clearing biologics.

Alfa Cytology's highly trained team has mastered the complex chelation chemistry of Indium-111 and provides custom-labeled antibodies and peptides in high purity, which are perfect for multi-day SPECT imaging and biodistribution studies. Fully customizable 111In-labeling approaches are available for your preclinical studies. If your project needs, feel free to contact one of our experts to discuss complex 111In-labeling strategies and their application in your preclinical research.

Reference

1. KAZUTA N, NAKASHIMA K, WATANABE H, et al. Effect of Linker Entities on Pharmacokinetics of (111)In-Labeled Prostate-Specific Membrane Antigen-Targeting Ligands with an Albumin Binder [J]. ACS pharmacology & translational science, 2024, 7(8): 2401-13.

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