Marion De Jong PhD, Presenter: Nothing to Disclose

Theodosia Maina, Abstract Co-Author: Nothing to Disclose

Berthold Nock, Abstract Co-Author: Nothing to Disclose

Radiopeptide drugs like radiolabeled octreotide-analogs are successfully being applied for tumor visualization and treatment. However, translation of this paradigm to other radiopeptide ligands has been severely hampered by their often-poor metabolic stability. We hypothesized a novel application -single co-injection of a specific enzyme inhibitor- to improve peptide bioavailability and hence tumor uptake in vivo.

The neutral endopeptidase inhibitor phosphoramidon (PA, 0.3mg) was injected with 111In-labeled somatostatin, gastrin and bombesin radiopeptides in different mouse models (healthy mice as well as tumor-bearing SCID and nude mice). PA is a potent (IC50 34 nM) and reversible competitive NEP-inhibitor. 4 and 24 h post injection, biodistribution as well as dynamic and static animal SPECT/CT imaging was performed.

We could provoke a remarkable and very significant rise (up to 40 times the control values) in the percentage of circulating intact 111In-labeled somatostatin, gastrin and bombesin radiopeptides in healthy mice after PA coinjection. Most importantly, this strategy resulted in a spectacular increase of radiolabel accumulation (up to 14 times the control values) in the different types of tumors xenografted in the mice. The improved tumor uptake could be clearly visualized by SPECT/CT as well.

Our findings open exciting new opportunities for the application of biodegradable peptide-drugs of either natural or synthetic origin as well as for the rationale design of in vivo stable analogs. They also provide a versatile tool for elucidating enzyme – peptide interactions.

not applicable yet

De Jong, M, Maina, T, Nock, B, Enzyme Inhibitors Impressively Enhance Tumor Uptake of Radiopeptides.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14014890.html