These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Radiometal-Dependent Biological Profile of the Radiolabeled Gastrin-Releasing Peptide Receptor Antagonist SB3 in Cancer Theranostics: Metabolic and Biodistribution Patterns Defined by Neprilysin.
    Author: Lymperis E, Kaloudi A, Sallegger W, Bakker IL, Krenning EP, de Jong M, Maina T, Nock BA.
    Journal: Bioconjug Chem; 2018 May 16; 29(5):1774-1784. PubMed ID: 29664606.
    Abstract:
    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 68Ga-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 68Ga to 111In/177Lu-label on the biological properties of resulting radiopeptides. Notably, the bioavailability of 111In/177Lu-SB3 in mice drastically deteriorated compared with metabolically robust 68Ga-SB3, and as a result led to poorer 111In/177Lu-SB3 uptake in GRPR-positive PC-3 xenografts. The peptide cleavage sites were identified by chromatographic comparison of blood samples from mice intravenously receiving 111In/177Lu-SB3 with each of newly synthesized 111In/177Lu-SB3-fragments. Coinjection of the radioconjugates with the neprilysin (NEP)-inhibitor phosphoramidon led to full stabilization of 111In/177Lu-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 68Ga/111In/177Lu-SB3 profiles in mice emphasizing the theranostic prospects of SB3 for clinical use.
    [Abstract] [Full Text] [Related] [New Search]