Podcast
Questions and Answers
What was the purpose of comparing data obtained from UHPLC and radio-TLC?
What was the purpose of comparing data obtained from UHPLC and radio-TLC?
- To analyze the standard deviations of the results.
- To validate the calibration of equipment.
- To determine the specific activity of Lu-177.
- To verify the agreement between the two analytic methods. (correct)
What factor is significant in achieving a radiochemical yield of over 90% for Lu-177?
What factor is significant in achieving a radiochemical yield of over 90% for Lu-177?
- Lower ligand concentrations.
- A twofold excess of ligand. (correct)
- A threefold excess of ligand. (correct)
- Higher radionuclidic purity of the metal.
Why were standard deviations computed but not reported in the figures?
Why were standard deviations computed but not reported in the figures?
- Due to a lack of statistical significance.
- Because the results were accurate enough without them.
- To avoid cluttering the figures with excessive information. (correct)
- To maintain clarity in presenting the data. (correct)
What was indicated to be a characteristic of the Y-90 used in the study?
What was indicated to be a characteristic of the Y-90 used in the study?
What was depicted in Fig. 1 of the results section?
What was depicted in Fig. 1 of the results section?
What was the primary aim of the study regarding Y- and Lu-DOTATATE yields?
What was the primary aim of the study regarding Y- and Lu-DOTATATE yields?
Which software was used for the calculations in the study?
Which software was used for the calculations in the study?
What conditions were maintained during the UHPLC analyses?
What conditions were maintained during the UHPLC analyses?
Which of the following metal contaminants was NOT mentioned as a part of the study?
Which of the following metal contaminants was NOT mentioned as a part of the study?
What condition related to the stability constants calculations was specified?
What condition related to the stability constants calculations was specified?
What are the competing cationic metals mentioned that can influence the radiolabeling yield of yttrium-90 and lutetium-177?
What are the competing cationic metals mentioned that can influence the radiolabeling yield of yttrium-90 and lutetium-177?
What was the molar ratio of DOTATATE to the metals used in the first set of experiments?
What was the molar ratio of DOTATATE to the metals used in the first set of experiments?
Which metal was expected to be a strong competitor but only partly influenced the incorporation?
Which metal was expected to be a strong competitor but only partly influenced the incorporation?
Which metals did not compete with Y 3+ and Lu 3+ in the formation of DOTATATE complexes?
Which metals did not compete with Y 3+ and Lu 3+ in the formation of DOTATATE complexes?
What method was used to analyze the final solutions in the first set of experiments?
What method was used to analyze the final solutions in the first set of experiments?
What amount of yttrium-90 or lutetium-177 chloride was added to the samples in the second set of experiments?
What amount of yttrium-90 or lutetium-177 chloride was added to the samples in the second set of experiments?
Which of the following metals was noted as a strong competitor at higher concentrations?
Which of the following metals was noted as a strong competitor at higher concentrations?
What was the main aim of this study on DOTA macrocyclic ligands?
What was the main aim of this study on DOTA macrocyclic ligands?
What method was used to assess the metal-DOTATATE complex formation?
What method was used to assess the metal-DOTATATE complex formation?
Which transition metals were selected for the study due to their high affinity for the DOTA ligand?
Which transition metals were selected for the study due to their high affinity for the DOTA ligand?
What ratio was maintained for the peptide/radionuclide during the reactions?
What ratio was maintained for the peptide/radionuclide during the reactions?
What was the main purpose of carrying out speciation calculations in the study?
What was the main purpose of carrying out speciation calculations in the study?
Which instrument was used for detecting radiochemical yields?
Which instrument was used for detecting radiochemical yields?
What theoretical foundations were used to calculate complex stability in the study?
What theoretical foundations were used to calculate complex stability in the study?
In the study, which of the following conditions was specified for the theoretical calculations?
In the study, which of the following conditions was specified for the theoretical calculations?
Which instrument was utilized for electrospray ionization–mass spectrometry in the study?
Which instrument was utilized for electrospray ionization–mass spectrometry in the study?
What was the pH buffer used in the preparation of the metals-DOTATATE samples?
What was the pH buffer used in the preparation of the metals-DOTATATE samples?
Which metal ion had the highest Log β value for the M+DOTA complex?
Which metal ion had the highest Log β value for the M+DOTA complex?
What concentration of HCl was used in the preparation of the samples?
What concentration of HCl was used in the preparation of the samples?
What was the temperature and duration for heating the test vials?
What was the temperature and duration for heating the test vials?
Which metal ion did not have a Log β value available for the M+DO3A complex?
Which metal ion did not have a Log β value available for the M+DO3A complex?
How much DOTATATE was added to each vial in nanomoles?
How much DOTATATE was added to each vial in nanomoles?
What method was used to analyze the samples after preparation?
What method was used to analyze the samples after preparation?
What was the purpose of adding varying amounts of metal cations to the vials?
What was the purpose of adding varying amounts of metal cations to the vials?
What is the maximum interference found for the coordination of Y 3+ and Lu 3+ with DOTATATE?
What is the maximum interference found for the coordination of Y 3+ and Lu 3+ with DOTATATE?
Which parameter is NOT mentioned as influencing the cations' affinity for DOTATATE?
Which parameter is NOT mentioned as influencing the cations' affinity for DOTATATE?
What is a characteristic feature of DOTATATE hexacoordinated complexes?
What is a characteristic feature of DOTATATE hexacoordinated complexes?
What is concluded about the role of ion size related to metal-DOTA complexes?
What is concluded about the role of ion size related to metal-DOTA complexes?
Which two cations showed comparable competition for coordination with DOTATATE?
Which two cations showed comparable competition for coordination with DOTATATE?
Why was the behavior of Pb 2+ not included in the analysis?
Why was the behavior of Pb 2+ not included in the analysis?
Which of the following metals is NOT mentioned as having an ionic radius relevant to the interference study with DOTATATE?
Which of the following metals is NOT mentioned as having an ionic radius relevant to the interference study with DOTATATE?
What makes DO3A an ineffective model for DOTATATE?
What makes DO3A an ineffective model for DOTATATE?
Flashcards
DOTATATE Complex
DOTATATE Complex
The DOTA molecule forms a complex with a metal ion through coordination bonds. The resulting DOTATATE complex is stable and highly specific, making it suitable for imaging and therapy.
Competing Cations
Competing Cations
The presence of other metals in the solution can compete with yttrium and lutetium, hindering the formation of the DOTATATE complex.
Influence of Metals on Coordination Yield
Influence of Metals on Coordination Yield
The yield of the DOTATATE complex is significantly affected by the presence of certain metals, even at low concentrations.
Metals studied
Metals studied
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Strong Competitors
Strong Competitors
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Moderate Competitors
Moderate Competitors
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Non-Competing Metals
Non-Competing Metals
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Analytical Methods Used
Analytical Methods Used
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Chromatography
Chromatography
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Ultra High-Performance Liquid Chromatography (UHPLC)
Ultra High-Performance Liquid Chromatography (UHPLC)
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Radiochemical Yield
Radiochemical Yield
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Thin Layer Chromatography (TLC)
Thin Layer Chromatography (TLC)
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Electrospray Ionization Mass Spectrometry (ESI-MS)
Electrospray Ionization Mass Spectrometry (ESI-MS)
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Metal Complex Stability
Metal Complex Stability
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Stability Constant
Stability Constant
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Metal Complex Formation
Metal Complex Formation
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Metal Ion Competition
Metal Ion Competition
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Influence of Metal Ions on DOTATATE Yield
Influence of Metal Ions on DOTATATE Yield
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Analytical Techniques for DOTATATE Complex
Analytical Techniques for DOTATATE Complex
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Y-90 and Lu-177 in DOTATATE Therapy
Y-90 and Lu-177 in DOTATATE Therapy
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Study Aim
Study Aim
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What is DOTATATE?
What is DOTATATE?
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Factors affecting Y/Lu-DOTATATE yields
Factors affecting Y/Lu-DOTATATE yields
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UHPLC technique
UHPLC technique
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What is Log β?
What is Log β?
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What was the objective of the study?
What was the objective of the study?
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Which metals were the strongest competitors?
Which metals were the strongest competitors?
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Were there any other metals that competed?
Were there any other metals that competed?
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Which metals did not show any competition?
Which metals did not show any competition?
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What method was used to analyze the complexes?
What method was used to analyze the complexes?
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How was the influence of competing metals tested?
How was the influence of competing metals tested?
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Why is understanding the influence of competing metals important?
Why is understanding the influence of competing metals important?
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Optimal Ionic Radius for DOTATATE Complex Formation
Optimal Ionic Radius for DOTATATE Complex Formation
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Strong Competitors for DOTATATE
Strong Competitors for DOTATATE
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Stability Constants Are Not Enough
Stability Constants Are Not Enough
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Metal Interference in DOTATATE Complex Formation
Metal Interference in DOTATATE Complex Formation
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DOTA is Not a Perfect Model for DOTATATE
DOTA is Not a Perfect Model for DOTATATE
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Ionic Radius and DOTATATE Complex Formation
Ionic Radius and DOTATATE Complex Formation
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Analytical Techniques Used for DOTATATE Complex Analysis
Analytical Techniques Used for DOTATATE Complex Analysis
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Kinetics and Stability of Metal-DOTA Complexes
Kinetics and Stability of Metal-DOTA Complexes
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Study Notes
Influence of Metallic Cations on Radiolabeling
- The study investigated the impact of competing cations on the labeling of DOTA with ⁰Y and ¹⁷⁷Lu.
- This competition is significant as DOTA can form stable complexes with various cations, affecting the reaction yield of ⁹⁰Y and ¹⁷⁷Lu-DOTATATE complexes.
- The aim was to evaluate the coordination yield of ⁹⁰Y and ¹⁷⁷Lu-DOTATATE complexes in the presence of various competing cationic impurities.
- Experiments were conducted using natural ⁹⁰Y and ¹⁷⁷Lu (20.4 nmol) with a 1:1 molar ratio of DOTATATE to metal.
- Metal competitors (Pb²⁺, Zn²⁺, Cu²⁺, Fe³⁺, Al³⁺, Ni²⁺, Co²⁺, Cr³⁺) were added to obtain samples with varying molar ratios relative to ⁹⁰Y or ¹⁷⁷Lu (0.1, 0.5, 1, 2, and 10).
- The solutions were analyzed using high-performance liquid chromatography (UHPLC) with an UV detector.
Radiolabeling Yield and Competition Studies
- Low concentrations of Zn²⁺, Cu²⁺, and Co²⁺ significantly influenced the coordination of Y³⁺ and Lu³⁺.
- Pb²⁺ and Ni²⁺ were strong competitors at higher concentrations.
- Fe³⁺ also demonstrated competition but its effect wasn't entirely dependent on the concentration.
- Al³⁺ and Cr³⁺ did not compete with ⁹⁰Y and ¹⁷⁷Lu in the formation of DOTATATE complexes.
Experimental Methods
- The experiments were performed in controlled conditions similar to clinical radiolabeling procedures.
- The reactions were carried out in triplicate.
- Ultra-high-performance liquid chromatography (UHPLC) was used to quantify the coordination yields.
- Thin layer chromatography (TLC) was used to confirm radiochemical yields, when ⁹⁰Y and ¹⁷⁷Lu were added to the samples.
- Spectroscopic methods (mass spectrometry) confirmed the identity of the complexes analyzed.
Results and Discussion
- The study used both measured data and theoretical calculations based on reported thermodynamic constants for DOTA and DO₃A to determine the yield.
- The results showed significant correlation between the observed radiochemical yields and the ionic radii of the metal contaminants.
- Contaminants with ionic radii between 0.73 and 0.75 Å (Cu²⁺, Zn²⁺, and Co²⁺) showed the strongest interference.
- The study showed low correlation between theoretical and experimental yields, highlighting the need for further detailed kinetic studies in these conditions.
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