Zirconium-89 radio-nanochemistry and its applications towards the bioimaging of prostate cancer

In recent years, the use of metallic isotopes for nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) has become an area of much interest. In particular, PET is a molecular imaging modality that relies on the detection of two antiparallel, co-linear gamma rays (511 keV) emitted when a positron undergoes annihilation with an electron. PET isotopes of interest in medical practice are numerous and their use depends on their half-lives and introduction in the compounds of interest. These include: nitrogen-13 (t_1/2 = 10 min), carbon-11 (t_1/2 = 20 min), fluorine-18 (t_1/2 = 110 min) and metallic isotopes such as gallium-68 (t_1/2 = 68 min), titanium-45 (t_1/2 = 3.08 h), copper-64 (t_1/2 = 12.7 h), manganese-52 (t_1/2 = 5.59 d) or zirconium-89 (t_1/2 = 3.3 d). ⁸⁹Zr has emerged as a promising isotope for radiotracer design and in vivo delivery, on basis of its ideal half-life matching the biological half-life of antibodies, antibody fragments and nanomedicines leading to high-resolution PET images for the pre-clinical and clinical investigations of a number of conditions including the prospective use in prostate cancers in the search of new diagnostic biomarkers. The availability of a plethora of chelators satisfying the coordination number of 8 such as siderophore-like chelators and recently nanoparticles conferring high kinetic and thermodynamic stabilities provides various designs and versatility in chemistry and radiochemistry. The aqueous chemistry of ⁸⁹Zr is certainly of high importance for antibody-based imaging due to the match between the physical half- life of the nuclide and the biological half-life of the targeting vector, but mostly if there are no small molecules with more rapid pharmacokinetics available. This mini-review highlights some of the recently accounted advantages and disadvantages of current biomolecule-tagging techniques and proposes subtle radiotracer design changes that may be introduced in order to obtain a highly efficient targeted imaging with zirconium-labelled chemical entities and nanoconstructs. These may be of relevance to preclinical and clinical research towards the diagnosis of cancer in general, whilst highlighting some of the prostate cancer targeting approaches from the recent ⁸⁹Zr-focused radiochemistry literature.