Promising Performance of 4HMS, a New Zirconium-89 Octadendate Chelator.

Over the last decade, the interest in zirconium-89 (89Zr) as a positron-emitting radionuclide increased considerably because of its standardized production and its physical half-life (78.41 h), which matches the biological half-life of antibodies and its successful use in preclinical and clinical applications. So far, desferrioxamine (DFO), a commercially available chelator, has been mainly used as a bifunctional chelating system. However, there are some concerns regarding the in vivo stability of the [89Zr]Zr-DFO complex. In this study, we report the synthesis of an acyclic N-hydroxy-N-methyl succinamide-based chelator (4HMS) with 8 coordination sites and our first investigations into the use of this new chelator for 89Zr complexation. In vitro and in vivo comparative studies with [89Zr]Zr-4HMS and [89Zr]Zr-DFO are presented. The 4HMS chelator was synthesized in four steps starting with an excellent overall yield. Both chelators were quantitatively labeled with 89Zr within 5-10 min at pH 7 and room temperature; the molar activity of [89Zr]Zr-4HMS exceeded (>3 times) that of [89Zr]Zr-DFO. [89Zr]Zr-4HMS remained stable against transmetalation and transchelation and cleared from most tissues within 24 h. The kidney, liver, bone, and spleen uptakes were significantly low for this 89Zr-complex. Positron emission tomography images were in accordance with the results of the biodistribution in healthy mice. Based on DFT calculations, a rationale is provided for the high stability of 89Zr-4HMS. This makes 4HMS a promising chelator for future development of 89Zr-radiopharmaceuticals.

Automated radiosynthesis of 68Ga for large-scale routine production using 68Zn pressed target.

Gallium-68 (68Ga) has attracted increasing interest in recent years due to the expanding clinical applications of 68Ga-based radiopharmaceuticals (Rahbar et al., 2017). 68Ga is mainly produced via 68Ge/68Ga generators that are limited in yield by the 68Ge activity (typically up to 1.85 GBq at calibration time). With the increased-demand of 68Ga in nuclear medicine for positron emission tomography (PET) imaging, there is a need for more efficient and robust production methods to obtain larger amounts of [68Ga]GaCl3 with high radionuclidic and radiochemical purity and apparent molar activity (AMA) for facilitating the distribution of 68Ga-based radiopharmaceuticals. The objectives of this study were to develop a fast and efficient process for the preparation of 68Zn-based solid targets and to optimize the critical parameters for the automated radiosynthesis of [68Ga]GaCl3 for large-scale routine production.