²²⁵Ac-Radiolabeling Service

Development of next-generation targeted alpha therapy is enabled by ²²⁵Ac-radiolabeling service, which involves the powerful alpha-emitting radionuclide actinium-225 conjugating to new targeting vectors like antibodies and peptides. Alfa Cytology, with the specialized skills in actinide chemistry and the required high-containment facilities, to deliver custom ²²⁵Ac-conjugation services, pairing the market with very stable and effective radiopharmaceuticals for advanced preclinical investigations.

Introduction to ²²⁵Ac Isotopes

One of the most promising therapeutic agents for targeted alpha therapy is a radioisotope, actinium-225 (²²⁵Ac). It is an alpha-emitter with a half-life of 10 days, having a therapeutic potency magnified due to the four high-energy alpha particles released during its decay cascade. These alpha particles, with their very short range in tissue, deposit a large amount of energy, produce lethal damage to cancer cells, and spare surrounding tissues, which are healthy. In the case of monoclonal antibodies and other large, slowly diffusing biologics, the actinium-225 isotope's 10-day half-life makes it very suited for labeling.

²²⁵Ac-Labeling for Radiopharmaceuticals

The incorporation of actinium-225 (²²⁵Ac) is essential for the development of ultra-high potency radiopharmaceuticals and targeted alpha therapy. It involves the chelation of ²²⁵Ac to targeting vectors such as antibodies or peptides. The radiopharmaceutical's potency is derived from the isotope's decay cascade that emits four alpha particles of significant energy within a sub-millimeter range. The localized cytotoxic effect can obliterate a tumor while preserving surrounding tissues. The 10-day half-life of the isotope is a perfect match for the pharmacokinetics of large biologics.

Fig.1 Bioconjugation of YS5 with Macropa-NCS and Macropa-PEG4/8-TFP ester followed by radiolabeling with ²²⁵Ac(NO3)3. (BOBBA K N, et al., 2024)

²²⁵Ac 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 ²²⁵Ac-Labeling

For the development of radiopharmaceuticals, the ²²⁵Ac isotope offers an advantage of destructive power coupled with micro-scale precision. The useful radiotherapeutic properties of ²²⁵Ac arise from its decay cascade, which delivers highly localized and potent alpha-particle radiation directly to targeted cancer cells.

Our Services

Alfa Cytology has the specialized know-how in actinide chemistry and the necessary high-containment structure to complete custom ²²⁵Ac-conjugation to a large number of biologics safely and effectively. This ability guarantees that highly stable, potent, and precisely characterized targeted alpha therapeutics are developed and delivered, ready for rigorous preclinical evaluation.

Custom ²²⁵Ac Conjugation Service

²²⁵Ac conjugation transforms novel targeting vectors, such as antibodies and peptides, into exceptionally potent alpha-emitting radiopharmaceuticals by employing specialized chemistry to stably attach the powerful alpha-generator, actinium-225.

Small-Molecule Radionuclide Conjugate (SMRC)

Antibody-Radionuclide Conjugate (ARC)

Peptide-Radionuclide Conjugate (PRC)

siRNA-Radionuclide Conjugate

Workflow for Developing ²²⁵Ac-Radiolabeled Antibody Conjugates

²²⁵Ac Custom Antibody Labeling

The construction of a ²²⁵Ac-radiolabeled antibody conjugate is a meticulous, multi-stage process to the achievement of a high-purity, stable, biologically efficient, and specifically targeted radiopharmaceutical. The development of our service is rooted in a well-defined scientific approach and high standards of service quality and reliability.

• Strategy & Reagent Selection: Start with a collaborative strategy session to confirm fundamental parameters. Since ²²⁵Ac is a hard metal ion with a large ionic radius, it requires very efficient chelators, mainly macrocyclic polyaminocarboxylates such as DOTA or TCMC, which provide a suitable coordination cage.
• Protocol Optimization: We analyze the best practices for integrating ²²⁵Ac into the immunoconjugate by empirically determining ideal conditions. These include adjusting pH, temperature, and time to optimize the radiochemical yield while ensuring the antibody's stability and minimizing radiolysis.
• Custom Radiosynthesis: To maintain consistency in processes, ensure operator safety, and guarantee reproducibility of the product, optimized radiolabeling protocols are executed in shielded hot cells employing automated synthesis modules.

Purification & Quality Control

The successful incorporation of ²²⁵Ac is verified after labeling the compound. Purity, compound stability, and correct isotopic labeling are confirmed using analytical techniques like liquid chromatography (LC), mass spectrometry (MS), and scintillation counting, to ensure that they must pass specific standards set for biological studies.

In Vitro Evaluation

In vitro tests are performed to evaluate the biological properties of the ²²⁵Ac-labeled radiopharmaceutical. This includes studying its interaction with target receptors, cellular uptake, metabolic stability, and other pharmacological properties.

In Vivo Evaluation

The last step focuses on in vivo testing to evaluate the pharmacokinetics, biodistribution, and overall behavior of the radiolabeled compound within the organism. By employing imaging techniques and radiometric analysis, the distribution of the ²²⁵Ac-labeled compound into multiple tissues is monitored, shedding light on potential therapeutic applications, safety, and tissue-specific targeting.

Applications of ²²⁵Ac-Radiolabeling

The applications of ²²⁵Ac-radiolabeling are driven by its unparalleled potency as an alpha-particle generator, enabling the development of groundbreaking radiopharmaceuticals designed to eradicate aggressive, metastatic, and treatment-resistant cancers.

Equipped with actinide chemistry expertise and high-containment facilities, Alfa Cytology is uniquely positioned to manage the intricacies of your ²²⁵Ac-labeling projects. We invite you to connect with our scientific team to discuss how our capabilities can help you accelerate the development of your targeted alpha therapy program.

Reference

1. BOBBA K N, BIDKAR A P, WADHWA A, et al. Development of CD46 targeted alpha theranostics in prostate cancer using (¹³⁴)Ce/(²²⁵)Ac-Macropa-PEG(₄)-YS5 [J]. Theranostics, 2024, 14(4): 1344-60.

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