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?

High radionuclidic purity. Signup and view all the answers

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

Chromatograms overlapping and relative retention times. Signup and view all the answers

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

To obtain a complete profile of yields related to specific variables Signup and view all the answers

Which software was used for the calculations in the study?

Hyss2006 (Hyperquad Simulation and Speciation) Signup and view all the answers

What conditions were maintained during the UHPLC analyses?

Equal quantities of ligand and metal with the same pH Signup and view all the answers

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

Silver(I) Signup and view all the answers

What condition related to the stability constants calculations was specified?

Hydroxocomplexes and complexes with acetate were included 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?

Zn 2+, Cu 2+, Co 2+ Signup and view all the answers

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

1 to 1 Signup and view all the answers

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

Fe 3+ Signup and view all the answers

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

Al 3+ and Cr 3+ Signup and view all the answers

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

Ultra high-performance liquid chromatography 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?

6 MBq Signup and view all the answers

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

Pb 2+ Signup and view all the answers

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

To evaluate the coordination yield of yttrium and lutetium-DOTATATE complexes. Signup and view all the answers

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

Ultra high-performance liquid chromatography Signup and view all the answers

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

Fe3+, Ni2+, Co2+, Cu2+, Zn2+ Signup and view all the answers

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

1:1 Signup and view all the answers

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

To elucidate factors affecting labeling yields Signup and view all the answers

Which instrument was used for detecting radiochemical yields?

Thin layer chromatography scanner Signup and view all the answers

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

Reported thermodynamic constants Signup and view all the answers

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

25°C Signup and view all the answers

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

LTQ Orbitrap XL Signup and view all the answers

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

pH 4.6 with sodium acetate Signup and view all the answers

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

Y 3+ Signup and view all the answers

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

0.05 M Signup and view all the answers

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

90°C for 30 min Signup and view all the answers

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

Al 3+ Signup and view all the answers

How much DOTATATE was added to each vial in nanomoles?

20.4 nmol Signup and view all the answers

What method was used to analyze the samples after preparation?

Ultra-High-Performance Liquid Chromatography (UHPLC) Signup and view all the answers

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

To compare their reaction with DOTATATE Signup and view all the answers

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

Metals with an ionic radius between 0.730 and 0.745 Å Signup and view all the answers

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

Temperature of the reaction Signup and view all the answers

What is a characteristic feature of DOTATATE hexacoordinated complexes?

Higher coordination numbers are expected for certain metals Signup and view all the answers

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

Ionic radius along with other parameters influences complex stability Signup and view all the answers

Which two cations showed comparable competition for coordination with DOTATATE?

Y 3+ and Lu 3+ Signup and view all the answers

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

Lack of data regarding its coordination number 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?

Mg 2+ Signup and view all the answers

What makes DO3A an ineffective model for DOTATATE?

It lacks suitable coordination geometry for metal binding Signup and view all the answers

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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Description

This quiz explores the effects of metallic cations on the radiolabeling efficiency of DOTA with ⁰Y and ¹⁷⁷Lu. It highlights experimental findings regarding coordination yields in the presence of various competing cations, as well as the analytical techniques employed. Test your understanding of the chemical interactions and implications in radiopharmacy.