MRI Contrast Agents and Imaging
OptiLink is versatile and has applications beyond PDT. Current contrast agents used in MRI (magnetic resonance imaging) lack sensitivity because they cannot be targeted specifically to organs in the body under investigation. They accumulate in the kidneys after imaging, where their gadolinium (Gd(III)) content sometimes leads to nephrotoxicity. OptiLink can overcome these problems.
Inserting a paramagnetic metal ion into photosensitiser molecules converts them from light-activated cancer therapeutic moieties into potential MRI contrast agents. After conjugating them to an scFv with OptiLink technology, the resulting multiply-loaded scFv becomes a targeted contrast agent for MRI imaging.
Initial tests demonstrate that even with the less magnetically susceptible metal ion manganese (III), the multiply-loaded scFv has a contrast signal at least comparable with a standard MRI contrast agent containing Gd(III) (see below).
The advantages here are that the scFv multiply-loaded MRI contrast agent is targetable, has potentially more favourable pharmacokinetics and pharmacodynamics compared to standard contrast agents, and the OptiLink platform ensures that the individual paramagnetic entities on the scFv do not magnetically interfere with one other, thus significantly enhancing their performance.
Ultimately, the OptiLink platform will enable multiple loading of scFv targeting moieties with both photosensitising and MRI contrast agents, providing a possible pipeline of novel targeted 'see and treat' agents to improve efficacy and tolerability of cancer treatment, significantly shorten tumour treatment times, and improve quality of life for patients.
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