PET image-guided in vivo biodistribution of drug delivery systems by means of 18F-ammonium trifluoroborate radiolabels

"Positron Emission Tomograhy (PET) is a powerful imaging technique capable of in vivo probing of biological processes and gaining ground as an accurate method for assessing drug biodistribution. Although fluorine-18 (18F) is the most popular PET radioniclide, its introduction into water-soluble macromolecules and biocompatible polymers remains a challenge. As a way to circumvent the classical, but often difficult, 18F-Carbon bond formation, the 18F-Boron unit presents an attractive alternative access via [19F]-to-[18F] halogen exchange (Hal-Ex), e.g. to form the [18F]-ammonium trifluoroborate (AMBF3) bioconjugates.
The team of Dr. Cuenca (IQS-URL) has a vast experience in the utilization of of boron-based entities, with a recent research line in the group centered on the synthesis and conjugation of an AMBF3 labels with two drug delivery platforms: a discrete-molecular defined entity (A) and a nanoparticle-based system (B). Specifically, A is an Abiotic self-assembled 3D cages as delivery systems for anticancer drug Cisplatin (with U. Cardiff and CICbiomaGUNE), while B is pBAEs-based polyplexes for gene therapy (with the groups of GEMAT, IQS and CICbiomaGUNE).
To date, the IQS-URL team has successfuly accomplished two phases: a) the synthesis and characterization of a ""clickable"" AMBF3 labels and their Cu-click conjugation to both delivery platforms, and b) for B the ability to complex DNA, the in vitro viability and cellular uptake of AMBF3-modified systems have being verified. The Cardiff team has characterized the cages A by DOSY NMR and HRMS and the CICBiomaGUNE lab. has corroborated the efficient isotopic 18F exchange of free ligands. As far as we know, we are a pioneer team in Spain on applying the isotopic labelling by 18F Hal-Ex. Hence, this proposal aims to tackle the most critical phase: the synthesis and fast 18F Hal-Ex of the delivery systems and their subsequent in vivo biodistribution imaging.
"

"Positron Emission Tomograhy (PET) is a powerful imaging technique capable of in vivo probing of biological processes and gaining ground as an accurate method for assessing drug biodistribution. Although fluorine-18 (18F) is the most popular PET radioniclide, its introduction into water-soluble macromolecules and biocompatible polymers remains a challenge. As a way to circumvent the classical, but often difficult, 18F-Carbon bond formation, the 18F-Boron unit presents an attractive alternative access via [19F]-to-[18F] halogen exchange (Hal-Ex), e.g. to form the [18F]-ammonium trifluoroborate (AMBF3) bioconjugates.
The team of Dr. Cuenca (IQS-URL) has a vast experience in the utilization of of boron-based entities, with a recent research line in the group centered on the synthesis and conjugation of an AMBF3 labels with two drug delivery platforms: a discrete-molecular defined entity (A) and a nanoparticle-based system (B). Specifically, A is an Abiotic self-assembled 3D cages as delivery systems for anticancer drug Cisplatin (with U. Cardiff and CICbiomaGUNE), while B is pBAEs-based polyplexes for gene therapy (with the groups of GEMAT, IQS and CICbiomaGUNE).
To date, the IQS-URL team has successfuly accomplished two phases: a) the synthesis and characterization of a ""clickable"" AMBF3 labels and their Cu-click conjugation to both delivery platforms, and b) for B the ability to complex DNA, the in vitro viability and cellular uptake of AMBF3-modified systems have being verified. The Cardiff team has characterized the cages A by DOSY NMR and HRMS and the CICBiomaGUNE lab. has corroborated the efficient isotopic 18F exchange of free ligands. As far as we know, we are a pioneer team in Spain on applying the isotopic labelling by 18F Hal-Ex. Hence, this proposal aims to tackle the most critical phase: the synthesis and fast 18F Hal-Ex of the delivery systems and their subsequent in vivo biodistribution imaging.
"