Podcast
Questions and Answers
What quality control measure is used to assess the radiochemical purity of the [225Ac]Ac-DOTA-peptide?
What quality control measure is used to assess the radiochemical purity of the [225Ac]Ac-DOTA-peptide?
What is the specified gamma counting RCP value validated for the [225Ac]Ac-DOTA-peptide using accelerator produced material?
What is the specified gamma counting RCP value validated for the [225Ac]Ac-DOTA-peptide using accelerator produced material?
Which technique is NOT utilized to report the radioisotopic composition of the [225Ac]Ac-DOTA-peptide?
Which technique is NOT utilized to report the radioisotopic composition of the [225Ac]Ac-DOTA-peptide?
What is the half-life of 227Ac, which is significant in the context of the 227/225Ac-labeled agents?
What is the half-life of 227Ac, which is significant in the context of the 227/225Ac-labeled agents?
Signup and view all the answers
How long post-separation is 227Th at equilibrium with 227Ac according to the Bateman equations?
How long post-separation is 227Th at equilibrium with 227Ac according to the Bateman equations?
Signup and view all the answers
What is one of the reasons that the quality control of alpha-emitting isotopes is considered challenging?
What is one of the reasons that the quality control of alpha-emitting isotopes is considered challenging?
Signup and view all the answers
What is the half-life of Actinium-225?
What is the half-life of Actinium-225?
Signup and view all the answers
Which of the following isotopes does not decay into a stable isotope but instead continues to produce alpha-emitting progenies?
Which of the following isotopes does not decay into a stable isotope but instead continues to produce alpha-emitting progenies?
Signup and view all the answers
What is an important consideration regarding the amount of activity required for alpha-emitting isotopes in vivo detection compared to therapy efficacy?
What is an important consideration regarding the amount of activity required for alpha-emitting isotopes in vivo detection compared to therapy efficacy?
Signup and view all the answers
When does secular equilibrium occur during the decay of Actinium-225?
When does secular equilibrium occur during the decay of Actinium-225?
Signup and view all the answers
Study Notes
Quality Control of Long-Lived Alpha-Emitting Radiopharmaceuticals
- Focus on Actinium-225/227, Thorium-227, and Radium-223 for quality control (QC).
- QC challenges for alpha-emitting isotopes due to complex detection methods and contaminants/progenies.
- Targeted Alpha Particle Therapy (TAPT) is effective due to high Linear Energy Transfer (LET) and short tissue path-length.
- Alpha particle emission leads to severe DNA damage: single and double-strand breaks.
Actinium-225 Overview
- Actinium-225 has a half-life of 9.92 days and is used in targeted constructs for radio-labeled therapies.
- Key decay products include 213Bi (45 min T½) and 221Fr (5 min T½) with significant gamma emissions.
- Secular equilibrium affects QC procedures, reaching after approximately 55 min and 6.5 hours for certain isotopes.
Actinium-225 Supply and Demand
- Current production capacity is low compared to growing research and industrial interest.
- Active production sites: Oak Ridge National Laboratories (USA), Rosatom (Russia), Institute for Transuranium Elements (Germany).
- Innovative methods are being developed to boost supply.
Quality Control Procedures
- QC processes for [225Ac]Ac-DOTA-peptide include ensuring radiochemical purity, chemical identity, and radioisotopic purity.
- Techniques employed: Thin Layer Chromatography (TLC), High-Performance Liquid Chromatography (HPLC), and gamma counting.
- Specific quality control metrics involve achieving radiochemical purity (RCP) greater than 99.9%.
Alternative Production Routes for Actinium-225
- Alternative methods involve using accelerator-produced Actinium-225, allowing for efficient detection of gamma emissions at specific energy levels.
- Gamma counting of the resulting compounds demonstrates RCP of 94.2%, indicating effective processing.
High Purity Germanium Analysis
- High Purity Germanium detectors are utilized to evaluate processed peptide fractions over time.
- Quantification of decay products, such as radium and thorium isotopes, helps confirm the stability and purity during processing.
Quantification Techniques
- Bateman equations are employed for the quantification of 227Ac in labeled agents, establishing a relationship to 227Th ratios based on decay.
- After approximately 100 days, 227Th reaches equilibrium with 227Ac, allowing for accurate content determination.
Challenges in Detection and Discrimination
- Discrimination between Thorium-227 and Radium-223 poses significant challenges due to overlapping gamma emissions.
- Automated measurements are necessary for effective organ distribution evaluations of radiopharmaceuticals and understanding dosimetry.
Innovations in Detection Methods
- Combining gamma counting with spectral deconvolution techniques improves the ability to achieve exclusive detection of Thorium-227.
- Ongoing calibration and efficiency evaluations improve measurement accuracy against NIST standards for both 223Ra and 227Th.
Conclusion
- Quality control of long-lived alpha-emitting radiopharmaceuticals remains critical for safe and effective therapeutic applications.
- Advances in detection methodologies, alongside increased production capabilities, are essential to meet rising demand and enhance patient safety in targeted therapies.### Pharmacokinetics and Organ Distribution in Mice
- Used 227Th/223Ra discrimination to study in vivo 223Ra ingrowth.
- Administered [227Th]Th-Trastuzumab via intravenous injection to naive female Swiss/Webster mice.
Organ Uptake Observations
-
227Th Uptake:
- Elevated in liver, decreased in spleen, low in bone.
-
223Ra In Vivo Ingrowth:
- Accumulated significantly in spleen and bones, but remained low in liver.
Theranostic Capabilities
- 227Th and 89Zr labeled Trastuzumab utilized the same chemical precursor.
- Comparison of injected activity per gram (% Injected Activity/gram) at 24 hours and 14 days revealed similar patterns for 227Th and 89Zr.
Quality Control of Alpha Emitting Isotopes
- Quality control presents challenges specific to alpha-emitting isotopes due to potential radiation safety considerations and material handling.### Equipment Requirements
- Imaging radiopharmaceuticals laboratory requires a TLC reader, dose calibrator, and gamma counter.
- High Purity Germanium (HpGe) detector is essential for precise measurements.
- An alpha spectrometer may be utilized in certain situations.
Isotope Considerations
- Adjustments needed for each isotope and its progenies.
- Must respect secular and transient equilibrium for accurate results.
- Calibration and cross-instrument checks are crucial for reliability and consistency.
Team Composition
- A multidisciplinary team is necessary for effective operation and research.
- Team includes professionals from different backgrounds, enhancing collaboration and expertise.
Acknowledgements and Funding
- Thorek Laboratory and Program for Quantitative Molecular Therapeutics received recognition.
- Contributions from diverse experts in fields such as chemistry, engineering, and molecular therapeutics.
- Group includes individuals with advanced degrees and affiliations from institutions like Moffitt Cancer Center and University of Iowa.
Notable Contributors
- Key figures include Dr. Nadia Benabdallah, Dr. Peng Lu, Dr. Mark McLaughlin, and Dr. Richard L. Wahl.
- Various contributors from cyclotron facilities and the Department of Chemistry at Washington University in St. Louis.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
