Activatable molecular cancer imaging probe

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have been investigating the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation, photon-induced electron transfer (PeT) and photo-truncation. In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal emitted using the aforementioned mechanisms. Given the wide range of photochemical mechanisms and properties, target-cell specific activatable probes possess considerable flexibility and can be adapted to specific diagnostic needs. From a translational viewpoint, including considerations of both the clinical value and regulatory approval requirements, several clinically applicable candidates including indocyanine green labeled antibodies or a small molecular gamma-glutamyltransferase activatable probe, which are designed to be used during surgical or endoscopic procedures, have been tested and under on-going Phase 2 trial. In these years, we have developed fluorescence camera devise for activatable probes as well as IR700, which is currently used for another project near infrared photoimmunotherapy. We are focusing on monitoring NIR-PIT therapeutic effects real time during therapy using fluorescence imaging that is the extension of the project. Due to the tough animal budget condition, the progress of this project is slowing down.