Evaluation of a Bispidine‐Based Chelator for Gallium‐68 and of the Porphyrin Conjugate as PET/PDT Theranostic Agent

Abstract

In this study a bispidine ligand has been applied to the complexation of gallium(III) and radiolabelled with gallium‐68 for the first time. Despite its 5‐coordinate nature, the resulting complex is stable in serum for over two hours, demonstrating a ligand system well matched to the imaging window of gallium‐68 positron emission tomography (PET). To show the versatility of the bispidine ligand and its potential use in PET, the bifunctional chelator was conjugated to a porphyrin, producing a PET/PDT‐theranostic, which showed the same level of stability to serum as the non‐conjugated gallium‐68 complex. The PET/PDT complex killed >90 % of HT‐29 cells upon light irradiation at 50 μm. This study shows bispidines have the versatility to be used as a ligand system for gallium‐68 in PET.

Unprecedented Kinetic Inertness for a Mn2+‐Bispidine Chelate: A Novel Structural Entry for Mn2+‐Based Imaging Agents

“…This scaffold has been previously investigated for the complexation of 64/67 Cu 2+ [12] and 68 Ga 3+ . [13] At hree dimensional representation of the putative structure of the MnL 1 complex is shown in Scheme 2.…”

Synthesis and characterization of a tetradentate bispidine-based ligand and its zinc(II) complex

“…Besides their wellestablished use in the field of catalysis, these unique structures have also captured the attention of the pharmaceutical community over the years. Recently, bispidines have been studied as ligands for radiopharmaceutical applications [15], but also as diagnostic and therapeutic agents for cancer [16,17].…”

Unprecedented Kinetic Inertness for a Mn2+‐Bispidine Chelate: A Novel Structural Entry for Mn2+‐Based Imaging Agents

“…Finally, L 1 can be readily functionalized for biological targeting via the lysine terminal amine. This scaffold has been previously investigated for the complexation of 64/67 Cu 2+[12] and 68 Ga 3+ . A three dimensional representation of the putative structure of the MnL 1 complex is shown in Scheme .…”

“…This scaffold has been previously investigated for the complexation of 64/67 Cu 2+ [12] and 68 Ga 3+ . [13] A three dimensional representation of the putative structure of the MnL1 complex is shown in Scheme 2. We evidence here that despite a moderate thermodynamic stability, MnL1 has a resistance to acid catalyzed dissociation and transmetalation which is unprecedented for a Mn 2+ chelate.…”