Dataset Information

Synthesis of DOTA-pyridine chelates for ⁶⁴Cu coordination and radiolabeling of ?MSH peptide.

ABSTRACT:

Background

⁶⁴Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x?=?1-4) that sequentially substitute carboxyl moieties with pyridyl moieties on a DOTA backbone.

Results

We found that the presence of pyridyl groups significantly increases ⁶⁴Cu labeling conversion yield, with DOTA-2Py, -3Py and -4Py quantitatively complexing ⁶⁴Cu at room temperature within 5?min (1?×?10^-?4?M). [⁶⁴Cu]Cu-DOTA-xPy (x?=?2-4) exhibited good stability in human serum up to 24?h. When challenged with 1000?eq. of NOTA, no transmetallation was observed for all three ⁶⁴Cu complexes. DOTA-xPy (x?=?1-3) were conjugated to a cyclized ?-melanocyte-stimulating hormone (?MSH) peptide by using one of the pendant carboxyl groups as a bifunctional handle. [⁶⁴Cu]Cu-DOTA-xPy-?MSH retained good serum stability (>?96% in 24?h) and showed high binding affinity (Ki?=?2.1-3.7?nM) towards the melanocortin 1 receptor.

Conclusion

DOTA-xPy (x?=?1-3) are promising chelators for ⁶⁴Cu. Further in vivo evaluation is necessary to assess the full potential of these chelators as a tool to enable further theranostic radiopharmaceutical development.

SUBMITTER: Yang H

PROVIDER: S-EPMC7803858 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Synthesis of DOTA-pyridine chelates for <sup>64</sup>Cu coordination and radiolabeling of αMSH peptide.

Yang Hua H Gao Feng F McNeil Brooke B Zhang Chengcheng C Yuan Zheliang Z Zeisler Stefan S Kumlin Joel J Zeisler Jutta J Bénard François F Ramogida Caterina C Schaffer Paul P

EJNMMI radiopharmacy and chemistry 20210113 1

<h4>Background</h4><sup>64</sup>Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x = 1-4) that sequentially substitute carboxyl moiet ...[more]

PMID: 33438075

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Project description:The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results:64Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion:64Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as the differentiation of malignant versus benign tumors based on absolute labeling uptake.

Dataset Information

Synthesis of DOTA-pyridine chelates for ⁶⁴Cu coordination and radiolabeling of ?MSH peptide.

Background

Results

Conclusion

Publications

Synthesis of DOTA-pyridine chelates for <sup>64</sup>Cu coordination and radiolabeling of αMSH peptide.

Similar Datasets

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Dataset Information

Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of ?MSH peptide.

Background

Results

Conclusion

Publications

Synthesis of DOTA-pyridine chelates for <sup>64</sup>Cu coordination and radiolabeling of αMSH peptide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Synthesis of DOTA-pyridine chelates for ⁶⁴Cu coordination and radiolabeling of ?MSH peptide.