Impact of Metallic Cations on Radiolabeling

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Questions and Answers

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?

  • 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?

  • 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?

<p>High radionuclidic purity. (D)</p> Signup and view all the answers

What was depicted in Fig. 1 of the results section?

<p>Chromatograms overlapping and relative retention times. (B)</p> Signup and view all the answers

What was the primary aim of the study regarding Y- and Lu-DOTATATE yields?

<p>To obtain a complete profile of yields related to specific variables (B)</p> Signup and view all the answers

Which software was used for the calculations in the study?

<p>Hyss2006 (Hyperquad Simulation and Speciation) (C)</p> Signup and view all the answers

What conditions were maintained during the UHPLC analyses?

<p>Equal quantities of ligand and metal with the same pH (D)</p> Signup and view all the answers

Which of the following metal contaminants was NOT mentioned as a part of the study?

<p>Silver(I) (C)</p> Signup and view all the answers

What condition related to the stability constants calculations was specified?

<p>Hydroxocomplexes and complexes with acetate were included (B)</p> Signup and view all the answers

What are the competing cationic metals mentioned that can influence the radiolabeling yield of yttrium-90 and lutetium-177?

<p>Zn 2+, Cu 2+, Co 2+ (B), Al 3+, Cr 3+, Fe 3+ (D)</p> Signup and view all the answers

What was the molar ratio of DOTATATE to the metals used in the first set of experiments?

<p>1 to 1 (C)</p> Signup and view all the answers

Which metal was expected to be a strong competitor but only partly influenced the incorporation?

<p>Fe 3+ (A)</p> Signup and view all the answers

Which metals did not compete with Y 3+ and Lu 3+ in the formation of DOTATATE complexes?

<p>Al 3+ and Cr 3+ (B)</p> Signup and view all the answers

What method was used to analyze the final solutions in the first set of experiments?

<p>Ultra high-performance liquid chromatography (B)</p> Signup and view all the answers

What amount of yttrium-90 or lutetium-177 chloride was added to the samples in the second set of experiments?

<p>6 MBq (A)</p> Signup and view all the answers

Which of the following metals was noted as a strong competitor at higher concentrations?

<p>Pb 2+ (A)</p> Signup and view all the answers

What was the main aim of this study on DOTA macrocyclic ligands?

<p>To evaluate the coordination yield of yttrium and lutetium-DOTATATE complexes. (D)</p> Signup and view all the answers

What method was used to assess the metal-DOTATATE complex formation?

<p>Ultra high-performance liquid chromatography (C)</p> Signup and view all the answers

Which transition metals were selected for the study due to their high affinity for the DOTA ligand?

<p>Fe3+, Ni2+, Co2+, Cu2+, Zn2+ (C)</p> Signup and view all the answers

What ratio was maintained for the peptide/radionuclide during the reactions?

<p>1:1 (B)</p> Signup and view all the answers

What was the main purpose of carrying out speciation calculations in the study?

<p>To elucidate factors affecting labeling yields (C)</p> Signup and view all the answers

Which instrument was used for detecting radiochemical yields?

<p>Thin layer chromatography scanner (A)</p> Signup and view all the answers

What theoretical foundations were used to calculate complex stability in the study?

<p>Reported thermodynamic constants (B)</p> Signup and view all the answers

In the study, which of the following conditions was specified for the theoretical calculations?

<p>25°C (D)</p> Signup and view all the answers

Which instrument was utilized for electrospray ionization–mass spectrometry in the study?

<p>LTQ Orbitrap XL (A)</p> Signup and view all the answers

What was the pH buffer used in the preparation of the metals-DOTATATE samples?

<p>pH 4.6 with sodium acetate (C)</p> Signup and view all the answers

Which metal ion had the highest Log β value for the M+DOTA complex?

<p>Y 3+ (C)</p> Signup and view all the answers

What concentration of HCl was used in the preparation of the samples?

<p>0.05 M (B)</p> Signup and view all the answers

What was the temperature and duration for heating the test vials?

<p>90°C for 30 min (D)</p> Signup and view all the answers

Which metal ion did not have a Log β value available for the M+DO3A complex?

<p>Al 3+ (A)</p> Signup and view all the answers

How much DOTATATE was added to each vial in nanomoles?

<p>20.4 nmol (A)</p> Signup and view all the answers

What method was used to analyze the samples after preparation?

<p>Ultra-High-Performance Liquid Chromatography (UHPLC) (C)</p> Signup and view all the answers

What was the purpose of adding varying amounts of metal cations to the vials?

<p>To compare their reaction with DOTATATE (C)</p> Signup and view all the answers

What is the maximum interference found for the coordination of Y 3+ and Lu 3+ with DOTATATE?

<p>Metals with an ionic radius between 0.730 and 0.745 Å (B)</p> Signup and view all the answers

Which parameter is NOT mentioned as influencing the cations' affinity for DOTATATE?

<p>Temperature of the reaction (A)</p> Signup and view all the answers

What is a characteristic feature of DOTATATE hexacoordinated complexes?

<p>Higher coordination numbers are expected for certain metals (A)</p> Signup and view all the answers

What is concluded about the role of ion size related to metal-DOTA complexes?

<p>Ionic radius along with other parameters influences complex stability (B)</p> Signup and view all the answers

Which two cations showed comparable competition for coordination with DOTATATE?

<p>Y 3+ and Lu 3+ (A)</p> Signup and view all the answers

Why was the behavior of Pb 2+ not included in the analysis?

<p>Lack of data regarding its coordination number (B)</p> Signup and view all the answers

Which of the following metals is NOT mentioned as having an ionic radius relevant to the interference study with DOTATATE?

<p>Mg 2+ (D)</p> Signup and view all the answers

What makes DO3A an ineffective model for DOTATATE?

<p>It lacks suitable coordination geometry for metal binding (C)</p> Signup and view all the answers

Flashcards

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

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

The yield of the DOTATATE complex is significantly affected by the presence of certain metals, even at low concentrations.

Metals studied

The study evaluated the impact of various metal ions, including zinc, copper, and cobalt, on the formation of DOTATATE complexes.

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Strong Competitors

Zinc, copper, and cobalt were found to strongly interfere with the formation of DOTATATE complexes, even at low concentrations.

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Moderate Competitors

Iron, lead, and nickel also showed competing behavior, but their influence was less pronounced than zinc, copper, and cobalt.

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Non-Competing Metals

Aluminum and chromium did not show any significant competition with yttrium and lutetium in the formation of the DOTATATE complex.

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Analytical Methods Used

The study employed analytical techniques such as ultra-high-performance liquid chromatography (UHPLC) and radio-thin layer chromatography (radio-TLC) to assess the coordination yield.

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Chromatography

A technique that separates components based on their interaction with a stationary phase and a mobile phase. It's widely used in chemistry and biochemistry for identifying, purifying and quantifying compounds.

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Ultra High-Performance Liquid Chromatography (UHPLC)

A type of chromatography that uses a high-performance liquid chromatography (HPLC) system with high pressure to separate analytes at very high speeds.

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Radiochemical Yield

The ratio of the amount of a specific compound in a sample to the total amount of all compounds in the sample. It indicates the relative abundance of a particular component.

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Thin Layer Chromatography (TLC)

A technique that uses a thin layer of absorbent material (like silica gel) to separate and visualize compounds based on their different affinities for the stationary phase.

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Electrospray Ionization Mass Spectrometry (ESI-MS)

A type of mass spectrometry that uses electrospray ionization to generate ions from molecules in solution. It provides information about the molecular weight and structure of the analyte.

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Metal Complex Stability

The tendency of a metal ion to form a complex with another molecule or ion. It's a measure of the strength of the interaction between the metal and its ligand.

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Stability Constant

A measure of the concentration of a chemical species in a solution at equilibrium. It reflects the relative amounts of reactants and products in a reversible reaction.

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Metal Complex Formation

A chemical process where a metal ion and a ligand combine to form a complex. These complexes can have different properties from the original components.

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Metal Ion Competition

Certain metal ions in the solution can compete with Yttrium (Y) and Lutetium (Lu) for binding to the DOTA molecule, preventing the formation of the desired DOTATATE complex. This competition can negatively impact the yield of the complex.

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Influence of Metal Ions on DOTATATE Yield

The presence of other metal ions, even at low concentrations, can significantly impact the formation of the DOTATATE complex. Some ions are strong competitors, significantly reducing the yield, while others have a lesser effect.

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Analytical Techniques for DOTATATE Complex

UHPLC (Ultra-High-Performance Liquid Chromatography) and Radio-TLC (Radio-Thin Layer Chromatography) are analytical techniques used in the study to determine the formation and purity of the DOTATATE complex.

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Y-90 and Lu-177 in DOTATATE Therapy

The radioactive isotopes Y-90 and Lu-177 are used in conjunction with the DOTATATE complex for targeted therapy in nuclear medicine. Due to different chemical properties, they require different chelator:metal ratios for optimal complex formation.

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Study Aim

The aim of this study is to get a complete understanding of how much Yttrium (Y) and Lutetium (Lu) are formed with DOTATATE, depending on the ratio of the radioactive metal, any metal impurities, and the conditions of the experiment.

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What is DOTATATE?

DOTATATE is a molecule that is used to deliver radioactive metals to specific parts of the body. This study focuses on complexes formed from Yttrium (Y) and Lutetium (Lu) with DOTATATE.

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Factors affecting Y/Lu-DOTATATE yields

The amount of Yttrium and Lutetium formed from DOTATATE depends on the ratio of these metals, the presence of other metal impurities, and the specific conditions used in the experiment. These conditions include factors like temperature, pH, and time.

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UHPLC technique

The researchers used a special technique called UHPLC (Ultra-High Performance Liquid Chromatography) to analyze the results. This technique helps them separate and identify different components in a mixture, like the DOTATATE complexes.

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What is Log β?

The stability of a metal complex with DOTATATE is measured by its equilibrium constant, represented as Log β.

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What was the objective of the study?

In this study, researchers tested the influence of various metal ions on the formation of DOTATATE complexes with Yttrium or Lutetium.

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Which metals were the strongest competitors?

Zinc, Copper, and Cobalt were found to significantly interfere with the formation of DOTATATE complexes, even at low concentrations.

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Were there any other metals that competed?

Iron, Lead, and Nickel also competed with Yttrium and Lutetium, but their influence was less pronounced compared to Zinc, Copper, and Cobalt.

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Which metals did not show any competition?

Aluminum and Chromium did not show any significant competition with Yttrium and Lutetium in the formation of DOTATATE complexes.

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What method was used to analyze the complexes?

The study used UHPLC (Ultra-High-Performance Liquid Chromatography) to analyze the metal-DOTATATE complexes and determine the percentage of the desired Yttrium or Lutetium complex.

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How was the influence of competing metals tested?

The experiment involved adding varying amounts of different metal ions to a solution containing DOTATATE and Yttrium or Lutetium, followed by heating and analysis using UHPLC.

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Why is understanding the influence of competing metals important?

The study aimed to understand how the presence of other metal ions influences the formation of DOTATATE complexes, specifically with Yttrium and Lutetium, which are used in nuclear medicine.

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Optimal Ionic Radius for DOTATATE Complex Formation

The formation of DOTATATE complexes is favoured for metal ions with an ionic radius of approximately 0.74 Angstroms.

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Strong Competitors for DOTATATE

Metals like copper, zinc, and cobalt significantly interfere with the formation of DOTATATE complexes, even at low concentrations. They compete with yttrium and lutetium for binding to DOTATATE.

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Stability Constants Are Not Enough

The study found that the stability constants of metal-DOTA complexes are not the only factor determining coordination yield. Other factors like the kinetics of the reaction and the stability of the metal-DOTA complex need consideration.

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Metal Interference in DOTATATE Complex Formation

The yield of DOTATATE complexes with yttrium and lutetium is significantly influenced by the presence of other metals in the solution. The presence of these metals can hinder the formation of DOTATATE complexes.

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DOTA is Not a Perfect Model for DOTATATE

DOTA is similar to DOTATATE but lacks the targeting peptide. Therefore, it is not a suitable model for DOTATATE.

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Ionic Radius and DOTATATE Complex Formation

The ionic radius of the metal is a key factor influencing its ability to form DOTATATE complexes. Metals with ionic radii around 0.74 Angstroms exhibit the strongest interference.

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Analytical Techniques Used for DOTATATE Complex Analysis

The study utilized analytical techniques like UHPLC to analyze the coordination yield of DOTATATE complexes.

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Kinetics and Stability of Metal-DOTA Complexes

The rate at which the metal-DOTA complex forms and how stable it is are also important factors in determining the coordination yield. These factors can be influenced by the specific properties of the metal ion.

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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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