Accurate imaging of the lymphatics is important for surgeons contemplating operations intended to repair misaligned lymphatic ducts in certain, rare, genetically-derived birth defects. A non-invasive imaging method was developed previously at the MIP using MRI gadolinium-based contrast agents and was shown to be highly effective in a size-relevant preclinical pig model. We have further refined the contrast agent and the imaging model system with a view to taking an optimized agent into first-in-human trials. We prepared polyamidoamine G5-dendrimers labeled with Gd (III) chelates using macrocyclic DOTA and acyclic DTPA. Both chelates were attached to the dendrimer using thiourea linkages in 80% and 55% conjugation yields, respectively. Radiolabeled analogs of both complexes were prepared using Gd containing radioactive 153Gd and used for biodistribution studies in mice. Both agents showed similar tissue retention profiles. We are further investigating longer-term biodistribution profiles, planning pre-clinical toxicology strategies and proceeding with scale-up and process development studies.

Conjugation of Gd(III) complexes to G5 dendrimer as MRI contrast agents for lymphangiography

244th National Meeting (2012)

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