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14C-Radiolabeling Service

The service for 14C radiolabeling provides accurate isotope labeling of compounds for thorough examination, facilitating studies on pharmacokinetics, metabolism, and distribution. Alfa Cytology has the necessary technology to perform 14C-Radiolabeling and produce preclinical research of the highest quality and greatest accuracy.

Introduction to 14C Isotopes

14C isotopes refer to carbon 14, which is a radioactive isotope of carbon and is used in various scientific studies, particularly in the fields of radiolabeling, metabolic studies, and pharmacokinetics. 14C has a half-life of 5730 years and hence is stable enough for long analysis but decays enough to successfully track compounds in biological systems. 14C is used for labeling various small molecules, peptides, and biologics, which helps in studying the absorption, distribution, metabolism, and excretion (ADME), and pharmacokinetics of the compounds for preclinical studies.

14C Radiolabeling: A Tool for Drug Discovery and Development

14C radiolabeling is one of the most important and fundamental techniques used in the preparation of radiopharmaceuticals, which assists in tracking the distribution of the drugs, the metabolism, and the pharmacokinetics. With the addition of the radioactive isotopes of carbon to a compound, a researcher has the ability to study the pharmacokinetics and biochemistry of the compound in a living system without altering the chemical structure of the compound. This is important in developing a drug to understand the interactions of a drug with a receptor.

Carbon-14 radiolabeling: a traceless tool for tracking organic molecules, supporting drug development and the agrochemical industry. Fig 1. Carbon-14 radiolabeling: a traceless tool for tracking organic molecules, supporting drug development and the agrochemical industry. (BABIN V, et al., 2022)

Advantages of 14C Labeling and Tracing Technology

High Sensitivity

14C has an extremely high detection sensitivity, reaching a maximum specific activity of 2.3 MBq/mmol (1.2 × 1011 dpm/mmol) and allowing detection of extremely low levels (ppt) of this radioisotope. In contrast, high-resolution mass spectrometry can only achieve sensitivity at the ppb level.

Reliable Experimental Results

Isotope-labeled tracer technology yields more reliable results than control experiments, as it is independent of matrix effects, background interference, and other analytical and/or interferences. The half-life of 14C is 5,370 years, which means that the correction for radioactive half-life is eliminated in experimental data.

Minimal Isotope Effect

When 14C replaces 12C atoms, the impact will be minimal on the chemical reactivity for the whole molecule. Meanwhile, the substitutive isotopism of hydrogen will considerably alter the physical and chemical properties, which can hinder the signs of the metabolism and the distributions of biological and environmental compounds.

High Labeling Stability

While performing labeling reactions, 3H tends to undergo exchange reactions with stable hydrogen in water, which leads to a loss of labeling. In contrast to this, carbon labeling positions are often on the molecular backbone, which ensures that the 14C labeling remains stable.

Our Services

Alfa Cytology provides services with unrivaled quality due to advanced know-how and state-of-the-art capabilities in 14C-radiolabeling for tracking compounds in various lines of research. Our services support highly accurate and dependable studies in pharmacokinetics, metabolism, and environmental studies.

Custom 14C Conjugation Service

Alfa Cytology offers custom 14C conjugation services, providing tailored solutions for the precise radiolabeling of compounds, including small molecules, antibodies, and other biologics, to meet specific research needs.

Scheme of 14C Radiosynthesis

Built upon a foundation of versatile and well-established synthetic methodologies, our capabilities are structured to handle a wide array of complex molecular targets. For more efficient and streamlined processes, we have structured our expertise in synthetic chemistry into three primary schemes that allow for specialization:

  • Synthetic Scheme I
    Specializing in the synthesis of derivatives for fatty acids, aromatic acids, and methanol, which are among the primary constituents for numerous organic syntheses.
  • Synthetic Scheme II
    Concentrated on the creation of alkyne derivatives and aromatic derivatives, which facilitate sophisticated coupling reactions and the synthesis of intricate molecular structures.
  • Synthetic Scheme III
    Committed to the synthesis of cyanamide, nitrile, and urea derivatives, which are important functional groups and are in key pharmaceutical active ingredients (APIs) and others.

Workflow for Developing 14C-Radiolabeled Small Molecule Conjugates

14C Custom Radiosynthesis

  • Design Labeling Position: Analyze the drug's structure to choose a position for the 14C label that is metabolically stable. We want to place the 14C label to the extent that it stays on the core scaffold and after metabolism, ensuring tracking of the maximal number of metabolites is possible.
  • Design Synthesis Route: This includes the creation of effective and scalable synthetic pathways that optimally and selectively target the incorporation of the 14C atom at specific sites of the molecule to enhance the radiochemical yield.
  • Custom Radiosynthesis: The specialized radiochemistry team carries out the 14C-labeling synthesis. The work is conducted in high-quality, well-controlled radioactive work laboratory environments, ensuring the reliability and excellence of all reactions performed.

Purification & Quality Control

  • Purification & Isolation: Employ high-performance liquid chromatography (HPLC) or similar techniques to extract and purify the target 14C-labeled compound from the reaction mixture.
  • Structure Confirmation: Confirmation is done by comparing to a "cold" (non-radioactive) standard of the compound and using mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) techniques.
  • Quality Control (QC) Certification:
    • Chemical Purity: Assessed using validated methods such as HPLC-UV and UPLC. We certify the absence of significant chemical impurities.
    • Stability Assessment: To ensure the product integrity since release and throughout your study use, we carry out stability studies under specified storage regulations (e.g., evaluating stability in solution at specified temperature and pH).
    • Radiochemical Purity: A critical parameter measured by radio-HPLC or radio-TLC. RCP confirms the percentage of total radioactivity attributable to the desired radiolabeled product.
    • Specific Activity: Determined using liquid scintillation counting (LSC) coupled with mass spectrometry (LC-MS). We ensure the specific activity corresponds with your research needs.

In Vivo Study

Systematically collect a complete set of biological samples at various time points post-dose, including:

  • Blood/Plasma: For pharmacokinetic (PK) analysis.
  • Urine & Feces: For mass balance and determination of excretion pathways.
  • Expired Air: To trap 14CO2 if the label is in a metabolically labile position.
  • Bile: For investigating hepatobiliary excretion in certain animal models.
  • Tissues: At the terminal timepoint in preclinical studies for quantitative whole-body autoradiography (QWBA).

Bioanalytical Sample Analysis

  • Total Radioactivity Measurement: Use a liquid scintillation counter (LSC) to measure total 14C radioactivity in all biological samples. This information is critical for calculating mass balance (recovery) and for constructing PK profiles.
  • Metabolite Profiling: Use HPLC with in-line radio-detection to analyze plasma, urine, and feces extracts. This produces a "radiochromatogram" displaying the parent drug and the approximate abundance of all principal metabolites.
  • Metabolite Identification: Integrate the radio-chromatography data with high-resolution mass spectrometry (LC-MS/MS) to identify the chemical structures of the primary metabolites observed.
  • Quantitative Whole-Body Autoradiography (QWBA): In preclinical research, the animal carcass is frozen, and whole-body sections are prepared and imaged using phosphor imaging to detect and quantify the 14C signal, thus mapping the distribution of the drug across all the organs and tissues.

Applications of 14C-Radiolabeling

Carbon-14 (14C) radiolabeling is a versatile and powerful method with applications across various scientific disciplines. Its unique properties make it invaluable for tracing and quantifying carbon-containing compounds in complex systems.

Pharmaceutical and Biochemical Research

  • Pharmacokinetic Studies (ADME)
  • Carbon-14 Breath Test
  • Enzyme and Metabolite Studies
  • More

Our Featured Products

Helicobacter pylori Urea Breath Test Kits

The practical application and trustworthiness of our labeling expertise and technology can be seen in our Helicobacter pylori diagnosis products. This product can accurately collect and quantify 14C-labeled CO2, which confirms H. pylori infection with great sensitivity and specificity.

Product Name Description
Helicobacter pylori Urea Breath Test Kits The principle that mammalian cells do not have urease, and H. pylori do have it in abundance, is the basis for our non-invasive breath test platform. After the oral administration of our 14C-labeled urea, any H. pylori bacteria present will hydrolyze it and release 14C-labeled carbon dioxide. This gas moves into the bloodstream and is exhaled.

Key Radiolabeled Intermediates

Having a stock of key carbon-14 building blocks helps us expedite our research timelines. Our stock includes key precursor materials such as Barium Carbonate [14C], Urea [14C], and Aniline [14C(U)] Hydrochloride. Additionally, we have some pre-synthesized, complex, labeled compounds like some amino acids, sugars, lipids, and sterols, which help us custom-synthesize projects.

Types Product Name
Radiolabeled Precursors Aniline [14C(U)] hydrochloride
Acetic acid (salt), [1-14C]
Barium carbonate [14C]
Benzene, [14C(U)]
Benzyl alcohol, [7-14C]
CuCN[14C]
Methanol[14C]
Methyl iodide, [14C]
NaCN[14C]
Propionic acid (salt), [1-14C]
Pyruvic acid (salt), [1-14C]
Acetyl chloride, [1-14C]
Bromoacetic acid, [1-14C]
Benzaldehyde, [carbonyl-14C]
Benzoic acid, [7-14C]
Carbon dioxide[14C]
Ethanol, [1-14C]
Formic acid (salt), [14C]
Glycine, [1-14C]
Urea[14C]
Thiourea, [14C]
And more
Radiolabeled Amino Acids Arginine L-[14C(U)]
Leucine, L-[14C(U)]
Glycine, [14C(U)]
Phenylalanine-L-[14C(U)]
Alanine, L-[14C(U)]
Glutamic Acid, L-[14C(U)]
Isoleucine, L-[14C(U)]
Lysine, L-[14C(U)]
Radiolabeled Sugars GLUCOSE, D-[14C(U)]
GLUCOSE, D-[6-14C]
XYLOSE, D-[14C(U)]
SUCROSE, [14C(U)]
GLUCOSE, D-[1-14C]
DEOXY-D-GLUCCOSE, 2-[1-14C]
GALACTOSE, D-[1-14C]
And more
Radiolabeled Lipids and Sterols GLYCEROL, [14C(U)]
CHOLESTEROL, [4-14C]
OLEIC ACID, [1-14C]
PALMITIC ACID, [1-14C]
…… …… ……

At Alfa Cytology, we are fully committed to the development and innovation of 14C radiolabeled services. We harness our considerable technical skills and state-of-the-art research to professionally facilitate progress in the. If you need any further information about our services, please get in touch with us.

Reference

  1. BABIN V, TARAN F, AUDISIO D. Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges [J]. JACS Au, 2022, 2(6): 1234-51.

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

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