Bifunctional Gallium-68 Chelators: Past, Present, and Future.

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Organic Chemistry

Background:

• Bifunctional chelates are crucial for developing radiopharmaceuticals, particularly for positron emission tomography (PET) imaging.
• Gallium-68 (68Ga) is a widely used radioisotope for PET imaging due to its favorable properties.
• The development of stable and efficient chelating agents is essential for successful radiolabeling with 68Ga.

Purpose of the Study:

• To review the development of bifunctional chelates for synthesizing 68Ga radiopharmaceuticals.
• To categorize and discuss the structural aspects, labeling parameters, and complex stability of various bifunctional chelates.
• To highlight chelates suitable for kit-type preparations and emerging promising derivatives.

Main Methods:

• Literature review and synthesis of existing knowledge on bifunctional chelates for 68Ga radiopharmaceuticals.
• Classification of chelates into macrocyclic, nonmacrocyclic, and chimeric groups.
• Analysis of chelate structure, 68Ga-labeling efficiency, and complex stability.

Main Results:

• Bifunctional chelates are categorized based on their structural motifs: macrocycles, nonmacrocycles, and chimeric derivatives.
• Key parameters for 68Ga-labeling and the stability of resulting complexes are discussed for relevant chelates.
• Certain nonmacrocyclic (e.g., THP-derivatives) and chimeric (e.g., DATA-derivatives) bifunctional chelates show particular promise for 68Ga radiopharmaceutical development and kit-type preparations.
• The use of Gallium-67 (67Ga) in place of 68Ga for some derivatives is also considered.

Conclusions:

• Bifunctional chelates are critical for advancing 68Ga radiopharmaceutical development.
• Nonmacrocyclic and chimeric chelates, including THP and DATA derivatives, are currently of significant interest due to their potential for efficient labeling and kit-formulations.
• Continued research into novel bifunctional chelates will further enhance the utility of 68Ga in nuclear medicine.