2018/04/17 by Emmanouil Lymperis, Aikaterini Kaloudi, Werner Sallegger +6
Medicine · Neuroscience · #Neuroendocrine Tumor Research Advances #Neuropeptides and Animal Physiology #Radiopharmaceutical Chemistry and Applications
paper · doi:10.1021/acs.bioconjchem.8b00225
openalex publication_date 2018/04/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Recent advances in oncology involve the use of diagnostic/therapeutic radionuclide-carrier pairs that target cancer cells, offering exciting opportunities for personalized patient treatment. Theranostic gastrin-releasing peptide receptor (GRPR)-directed radiopeptides have been proposed for the management of GRPR-expressing prostate and breast cancers. We have recently introduced the PET tracer 68 Ga-SB3 (SB3, DOTA- p -aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), a receptor-radioantagonist that enables the visualization of GRPR-positive lesions in humans. Aiming to fully assess the theranostic potential of SB3, we herein report on the impact of switching 68 Ga to 111 In/ 177 Lu-label on the biological properties of resulting radiopeptides. Notably, the bioavailability of 111 In/ 177 Lu-SB3 in mice drastically deteriorated compared with metabolically robust 68 Ga-SB3, and as a result led to poorer 111 In/ 177 Lu-SB3 uptake in GRPR-positive PC-3 xenografts. The peptide cleavage sites were identified by chromatographic comparison of blood samples from mice intravenously receiving 111 In/ 177 Lu-SB3 with each of newly synthesized 111 In/ 177 Lu-SB3-fragments. Coinjection of the radioconjugates with the neprilysin (NEP)-inhibitor phosphoramidon led to full stabilization of 111 In/ 177 Lu-SB3 in peripheral mouse blood and resulted in markedly enhanced radiolabel uptake in the PC-3 tumors. In conclusion, in situ NEP-inhibition led to indistinguishable 68 Ga/ 111 In/ 177 Lu-SB3 profiles in mice emphasizing the theranostic prospects of SB3 for clinical use.