Progress of Coordination and Utilization of Zirconium-89 for Positron Emission Tomography (PET) Studies

Abstract

Radiometals have been commonly used in medical applications, and utilization of such metals continues to be an attractive research area. In particular, a variety of radiometals have been developed and implemented for molecular imaging. For such applications, 89 Zr has been one of the most interesting radiometals currently used for tumor targeting. Several chemical ligands were developed as 89 Zr chelators, and new coordinating methods have also been developed more recently. In addition, immunopositron emission tomography (PET) studies using 89 Zr-labeled monoclonal antibodies have been performed by several scientists. In this review, recent advances to the coordination of 89 Zr and the utilization of 89 Zr in PET studies are described.

Evaluation of the Tetrakis(3-Hydroxy-4-Pyridinone) Ligand THPN with Zirconium(IV): Thermodynamic Solution Studies, Bifunctionalization, and in Vivo Assessment of Macromolecular 89Zr-THPN-Conjugates

“…The supernatant was removed and the precipitate was dried in vacuo to give the title compound 8 as a white hydrochloride salt in ∼94% yield (243 mg, ∼176 μmol). (9). In a Schlenk flask under inert atmosphere, compound 8 (∼240 mg, ∼ 174 μmol) was dissolved in methanol (∼20 mL), and Pd/C was added (10% w/w, 19.6 mg, 18.4 μmol).…”

Strategic, feasibility, economic, and cultural aspects of phase 0 approaches

“…PET tracers to measure target occupancy of investigational drugs should be developed in parallel to drug discovery programs, if possible, to ensure their timely availability when the drug enters clinical testing. The use of PET to assess post‐target modulation is particularly common in anticancer drug development using [ 17 F]FDG to measure tumor metabolic activity or other pathway‐specific radiotracers 102,103 …”

“…The use of PET to assess post‐target modulation is particularly common in anticancer drug development using [ 17 F]FDG to measure tumor metabolic activity or other pathway‐specific radiotracers. 102 , 103 …”

Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand

“…The synthesis of the chelating pharmacophore CA-PSMA (10) is presented in Scheme 2. The room temperature O-alkylation of the chelidamic acid diethyl ether (4) [19] with benzylic bromide (5) [20] yielded the corresponding isothiocyanate (6), which was coupled with (7) and synthesized as described by Maresca et al [21] to yield (8). The ethyl esters were saponified with LiOH in tetrahydrofuran (THF)/water, giving (9) followed by removal of the tert-butyl groups with trifluoroacetic acid (TFA) in dichloromethane (DCM) to give CA-PSMA (10).…”

“…Among these, radiometals are particularly attractive as they combine widely varying half-lives with an ease of radiolabeling via kit formulations [4]. While the radionuclides 68 Ga and 82 Rb still dominate the traditional clinical setting, the use of 64 Cu [5] and 89 Zr [6] is on the rise in university clinics and clinical trials, and a plethora of PET tracers based on more unconventional PET radiometals such as 44 Sc, 45 Ti, 55 Co, and 86 Y are in development [7]. The radionuclide 45 Ti occupies a special place among unconventional PET radiometals, featuring 85% β + decay, negligible secondary radiation, and low β + endpoint energy (1.04 MeV), which translates into high spatial resolution as evidenced by sharp Derenzo phantom images [8][9][10].…”