1 research outputs found
Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding
Positron
emission tomography (PET) as well as optical imaging (OI)
with peptide receptor targeting probes have proven their value for
oncological applications but also show restrictions depending on the
clinical field of interest. Therefore, the combination of both methods,
particularly in a single molecule, could improve versatility in clinical
routine. This proof of principle study aims to show that a chelator,
Fusarinine C (FSC), can be utilized as scaffold for novel dimeric
dual-modality imaging agents. Two targeting vectors (a minigastrin
analogue (MG11) targeting cholecystokinin-2 receptor overexpression
(CCK2R) or integrin α<sub>V</sub>β<sub>3</sub> targeting
cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7)
were conjugated to FSC. The probes were efficiently labeled with gallium-68
and in vitro experiments including determination of logD, stability,
protein binding, cell binding, internalization, and biodistribution
studies as well as in vivo micro-PET/CT and optical imaging in U-87MG
α<sub>V</sub>β<sub>3</sub>- and A431-CCK2R expressing
tumor xenografted mice were carried out. Novel bioconjugates showed
high receptor affinity and highly specific targeting properties at
both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies
revealed specific tumor uptake accompanied by slow blood clearance
and retention in nontargeted tissues (spleen, liver, and kidneys)
leading to visualization of tumors at early (30 to 120 min p.i.).
Excellent contrast in corresponding optical imaging studies was achieved
especially at delayed time points (24 to 72 h p.i.). Our findings
show the proof of principle of chelator scaffolding for hybrid imaging
agents and demonstrate FSC being a suitable bifunctional chelator
for this approach. Improvements to fine-tune pharmacokinetics are
needed to translate this into a clinical setting