Radiopharmaceuticals for Imaging in Oncology with Special Emphasis on Positron-Emitting Agents

A comparative evaluation of the chelators H 4 octapa and CHX-A″-DTPA with the therapeutic radiometal 90 Y

“…Regardless of the identity of the metal, any radiopharmaceutical labeled with a metallic isotope must have a suitable chelator attached to the targeting vector (e.g., peptide, antibody) to facilitate the stable coordination of the radiometal ion [9,23–25]. The acyclic chelating ligand H 4 octapa (Fig.…”

What a Difference a Carbon Makes: H4octapa vs H4C3octapa, Ligands for In-111 and Lu-177 Radiochemistry

“… 1 − 10 The modular and versatile nature of these systems allows for a continually increasing number of routinely produced radiometals to be harnessed for single photon emission computed tomography (SPECT), positron emission tomography (PET), and therapy (e.g., Auger electron, β – , α). 1 − 10 Radiometal-based radiopharmaceuticals are typically broken down into several modules and can be assembled in many permutations for a high degree of customization: the targeting vector (e.g., peptide, antibody, nanoparticle) is selected for site-specific delivery to a chosen biological target or compartment; the bifunctional chelator (BFC) is selected for optimal stability and radiolabeling properties with the chosen radiometal; the bioconjugation method is selected based on the reactivity and functional groups available on the bifunctional chelator and targeting vector; and, finally, the radiometal is selected for its decay characteristics. 1 − 9 Even subtle changes to the ligand structure, site of conjugation, and donor arms of ligands can cause drastic changes to their radiolabeling properties and the stability of their radiometal complexes.…”

“…These ligand alterations can include the addition of functional groups to allow for conjugation with targeting vectors (e.g., p -benzyl-isothiocyanate, maleimide, activated esters), changes to ligand donor arms and ligand denticity (e.g., peptide coupling to a carboxylate donor arm), and changing ligand donor types (e.g., changing primary amines to secondary amines, or methylenephosphonates for carboxylates), and the effects of these changes on radiolabeling and stability properties can be significant. 1 − 10 The difference in stability and radiolabeling kinetics between acyclic and macrocyclic ligands is often significant, as macrocycles provide a degree of preorganization of the metal binding cavity, which provides a strong entropic incentive for metal complexation, although typically at the cost of slow reaction kinetics. 11 − 13 There are a number of competent and well-studied bifunctional chelators available for use; however, none are without shortcomings, and for purposes ranging from enhancing radiolabeling kinetics to enhancing kinetic inertness and in vivo stability, development of new bifunctional chelators is an important field of study.…”

“…The product (9) was isolated as yellow solid (2.34 g, 9.86 mmol, ∼83%). (10). Compound 9 (1.99 g, 8.40 mmol) was added to a two-necked round-bottomed flask under argon gas, and an addition funnel was attached.…”

“…In recent years, radiometal-based radiopharmaceuticals have become increasingly appreciated for their potential in diagnostic and therapeutic medicine. − The modular and versatile nature of these systems allows for a continually increasing number of routinely produced radiometals to be harnessed for single photon emission computed tomography (SPECT), positron emission tomography (PET), and therapy (e.g., Auger electron, β – , α). − Radiometal-based radiopharmaceuticals are typically broken down into several modules and can be assembled in many permutations for a high degree of customization: the targeting vector (e.g., peptide, antibody, nanoparticle) is selected for site-specific delivery to a chosen biological target or compartment; the bifunctional chelator (BFC) is selected for optimal stability and radiolabeling properties with the chosen radiometal; the bioconjugation method is selected based on the reactivity and functional groups available on the bifunctional chelator and targeting vector; and, finally, the radiometal is selected for its decay characteristics. − Even subtle changes to the ligand structure, site of conjugation, and donor arms of ligands can cause drastic changes to their radiolabeling properties and the stability of their radiometal complexes. These ligand alterations can include the addition of functional groups to allow for conjugation with targeting vectors (e.g., p -benzyl-isothiocyanate, maleimide, activated esters), changes to ligand donor arms and ligand denticity (e.g., peptide coupling to a carboxylate donor arm), and changing ligand donor types (e.g., changing primary amines to secondary amines, or methylenephosphonates for carboxylates), and the effects of these changes on radiolabeling and stability properties can be significant. − The difference in stability and radiolabeling kinetics between acyclic and macrocyclic ligands is often significant, as macrocycles provide a degree of preorganization of the metal binding cavity, which provides a strong entropic incentive for metal complexation, although typically at the cost of slow reaction kinetics. − There are a number of competent and well-studied bifunctional chelators available for use; however, none are without shortcomings, and for purposes ranging from enhancing radiolabeling kinetics to enhancing kinetic inertness and in vivo stability, development of new bifunctional chelators is an important field of study. …”