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Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

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Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding.

Dominik Summer¹, Leo Grossrubatscher¹, Milos Petrik²

¹Department of Nuclear Medicine, Medical University Innsbruck , Anichstrasse 35, A-6020 Innsbruck, Austria.

Bioconjugate Chemistry

|May 3, 2017

Summary

This study demonstrates Fusarinine C as a scaffold for dual-modality imaging agents, combining Positron Emission Tomography and Optical Imaging for enhanced tumor visualization. Further pharmacokinetic optimization is needed for clinical translation.

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Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling

Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling

Published on: September 20, 2016

Area of Science:

Biomedical imaging
Radiochemistry
Molecular imaging

Background:

Positron Emission Tomography (PET) and Optical Imaging (OI) are valuable in oncology but have limitations.
Combining PET and OI modalities, ideally in a single molecule, could enhance versatility in clinical practice.

Purpose of the Study:

To demonstrate Fusarinine C (FSC) as a scaffold for novel dimeric dual-modality imaging agents.
To create and evaluate bioconjugates for targeting cholecystokinin-2 receptor (CCK2R) or integrin αVβ3.

Main Methods:

Conjugation of targeting vectors (minigastrin analogue or RGD peptides) and a near-infrared fluorophore to FSC.
Labeling with Gallium-68 and conducting in vitro assays (stability, binding, internalization) and in vivo micro-PET/CT and optical imaging in tumor xenografts.

Main Results:

Novel bioconjugates exhibited high receptor affinity and specific targeting.
Micro-PET/CT showed specific tumor uptake with early visualization (30-120 min p.i.), but also off-target retention.
Optical imaging provided excellent contrast, particularly at delayed time points (24-72 h p.i.).

Conclusions:

Fusarinine C serves as a suitable bifunctional chelator for developing hybrid imaging agents.
This study provides proof of principle for chelator scaffolding in dual-modality imaging.
Pharmacokinetic improvements are necessary for clinical application.