Immuno-positron emission tomography (immunoPET) with ⁸⁹Zr-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. The most commonly used chelator for ⁸⁹Zr is desferrioxamine (DFO). Preclinical studies have shown that DFO is not an ideal chelator because the ⁸⁹Zr–DFO complex is partly unstable in vivo, which results in the release of ⁸⁹Zr from the chelator and the subsequent accumulation of ⁸⁹Zr in bone. This bone accumulation interferes with accurate interpretation and quantification of bone uptake on PET images. Therefore, there is a need for novel chelators that allow more stable complexation of ⁸⁹Zr. In this Review, we will describe the most recent developments in ⁸⁹Zr radiochemistry, including novel chelators and site-specific conjugation methods.

Currently, the most commonly used chelator for labelling antibodies with ⁸⁹Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the ⁸⁹Zr-DFO complex results in release of ⁸⁹Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the ⁸⁹Zr radiometal. The aim was to compare the in vitro and in vivo stability of [⁸⁹Zr]Zr-DFOcyclo*, [⁸⁹Zr]Zr-DFO* and [⁸⁹Zr]Zr-DFO.

The synthesis and the photophysical studies of the first bodipy–DOTA and its In(III), Ga(III) and Cu(II) complexes are reported. The introduction of an isothiocyanate handle generates a new bimodal imaging agent capable of both optical and nuclear imaging.

Actinium-225 (²²⁵Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with ²²⁵Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with ²²⁵Ac at pH 5.6 (30 min at 70 °C), and in vitro stability was evaluated. In vitro cytotoxicity was assessed in U-87 MG cancer cells, and in vivo biodistribution was performed by intravenous and intratumoral administration of [²²⁵Ac]²²⁵Ac-Au@TADOTAGA in U-87 MG tumor-bearing mice. A preliminary study to assess therapeutic efficacy of the intratumorally-injected radio-nanomedicine was performed over a period of 22 days, while the necrotic effect on tumors was evaluated by a histopathology study. We have shown that [²²⁵Ac]²²⁵Ac-Au@TADOTAGA resulted in the retardation of tumor growth after its intratumoral injection in U87MG tumor-bearing mice, even though very low activities were injected per mouse. This gold nanoparticle radiopharmaceutical could be applied as an unconventional brachytherapy in injectable form for local radiation treatment of cancer.