The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker

Abstract

Therapeutic radiopharmaceuticals have been researched extensively in the last decade as a result of the growing research interest in personalized medicine to improve diagnostic accuracy and intensify intensive therapy while limiting side effects. Radiometal-based drugs are of substantial interest because of their greater versatility for clinical translation compared to non-metal radionuclides. This paper comprehensively discusses various components commonly used as chemical scaffolds to build radiopharmaceutical agents, i.e., radionuclides, pharmacokinetic-modifying linkers, and chelators, whose characteristics are explained and can be used as a guide for the researcher.

Radiolabeled Iron Oxide Nanoparticles as Dual Modality Contrast Agents in SPECT/MRI and PET/MRI

“…Gallium 3+ is hexacoordinated to DOTA, resulting in an N 4 O 2 distorted octahedron. It has been shown that the large size of the macrocycle is not ideal for Ga 3+ complexation (logK 1 = 26.05) [ 78 ]; however, Ga 3+ complexes with DOTA exhibit high thermodynamic stability (logK ML = 21.3) and have excellent in vivo stability [ 79 ]. Despite the limitations associated with the use of DOTA in biomolecule radiolabeling, to this day two of the four 68 Ga-based radiopharmaceuticals in clinical practice are based on the DOTA chelator.…”

Effect of metal complexation on the radiolytic stability of DOTA

“…These radiopharmaceuticals provide imaging within 24 hours of administration. In this context, 89 Zr is currently being studied for PET [2][3][4][5][6][7][8][9][10][11][12] applications and has received considerable attention in radioimmunotherapy applications because of its favourable decay characteristics and half-life period (t 1/2 = 78.4 h) making it useful for labelling monoclonal antibodies. 13 To deliver 89 Zr to a given target, a powerful chelator must be bound to the tetravalent metal ion to prevent the release of the radionuclide into the human body.…”

Interaction of Radiopharmaceuticals with Somatostatin Receptor 2 Revealed by Molecular Dynamics Simulations

“…Most efforts of modern medicine are addressed toward personalized medicine, in which each patient is treated according to the molecular features of the disease of interest. , In this contest, radiopharmaceuticals have been extensively used to specifically target unhealthy tissues. , According to the decay properties of the radionuclide, compounds can be employed for diagnostic or therapeutic purposes, or both (theranostics) . Radionuclides emitting γ or β+ ( e.g.…”

“…3,4 According to the decay properties of the radionuclide, compounds can be employed for diagnostic or therapeutic purposes, or both (theranostics). 5 Radionuclides emitting γ or β+ (e.g., 111 In and 68 Ga) are exploited for imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET), respectively, while those emitting βor α (e.g., 177 Lu and 211 At) are used for therapeutic treatments. 6 In this last case, after the binding of a radiopharmaceutical to the given target and its subsequent internalization, a cytotoxic dose of radiation is delivered to the cancer cell.…”