Several limitations of ¹⁸F and other non-metallic isotopes have been emphasized by the development of macromolecular biotargeting agents for cancer, including peptides, antibodies, fragments and oligonucleotides, which typically have biological half-lives that are much longer than the radioactive half-life of ¹⁸F. Based on the ¹⁸F-FDG success story, we can wonder whether all critical criteria are or can be fulfilled for the radiometallated bioconjugates to start out from the crowd and which metals have the best chance of success. In this paper we give a brief overview of radiometal isotopes having the potential for PET imaging in terms of physical properties, production capacity and associated chemistry.

Fluorescent probes are commonly used in studying G protein-coupled receptors in living cells; however their application to the whole animal receptor imaging is still challenging. To address this problem, we report the design and the synthesis of the first near-infrared emitting fluorogenic dimer with environment-sensitive folding. Due to the formation of non-fluorescent H-aggregates in an aqueous medium, the near-infrared fluorogenic dimer displays a strong turn-on response (up to 140-fold) in an apolar environment and exceptional brightness: 56% quantum yield and ≈444 000 M⁻¹ cm⁻¹ extinction coefficient. Grafted on a ligand of the oxytocin receptor, it allows the unprecedented background-free and target-specific imaging of the naturally expressed receptor in living mice.

Positrons are widely used in molecular imaging through the Positron Emission Tomography (PET) imaging technique. However PET only reconstruct the distribution of the positron emitting radioisotopes, and because the β+ isotopes are linked to a vector molecule, the distribution of β+ isotopes is correlated to the distribution of a given biological function. Positron-electron annihilation can transit through a meta-stable called positronium, which can exist in two spin states: the single state -parapositronium -and the triplet state -orthopositronium. The orthopositronium lifetime (τoPs), formation probabilities and decay modes are sensitive to the physical and chemical state of the neighboring medium and could therefore provide information on the tissues themselves during a PET acquisition. However, traditional PET only relies on the detection of the two annihilation photons, therefore the lifetime and annihilation higher multiplicity annihilations are not accessible to such PET paradigm. This review will present some of the use cases of positronium as a specific signature for event selection in astrophysics and particle physics, and as a probe for the microscopic state of materials and tissues. These usages of positronium highlight the interest for positronium for diagnostic in medical science, the projects for using positronium in upcoming PET tomographs are then presented.

⁶⁴CuCl₂ is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of ⁶⁴CuCl₂ in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. ¹⁸F-FDG was used as a comparator. Twenty-two animals were imaged 7–9 days following 4T1-cell implantation inside mammary glands. Dynamic ⁶⁴CuCl₂ µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning ¹⁸F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor ⁶⁴CuCl₂ accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle ⁶⁴CuCl₂ accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The ¹⁸F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. ⁶⁴CuCl₂ PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.