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Issue 37, 2012
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Dual-targeting conjugates designed to improve the efficacy of radiolabeled peptides

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Abstract

Radiolabeled regulatory peptides are useful tools in nuclear medicine for the diagnosis (imaging) and therapy of cancer. The specificity of the peptides towards GPC receptors, which are overexpressed by cancer cells, and their favorable pharmacokinetic profile make them ideal vectors to transport conjugated radionuclides to tumors and metastases. However, after internalization of the radiopeptide into cancer cells and tumors, a rapid washout of a substantial fraction of the delivered radioactivity is often observed. This phenomenon may represent a limitation of radiopeptides for clinical applications. Here, we report the synthesis, radiolabeling, stability, and in vitro evaluation of a novel, dual-targeting peptide radioconjugate designed to enhance the cellular retention of radioactivity. The described trifunctional conjugate is comprised of a Tc-99m SPECT reporter probe, a cell membrane receptor-specific peptide, and a second targeting entity directed towards mitochondria. While the specificity of the first generation of dual-targeting conjugates towards its extracellular target was demonstrated, intracellular targeting could not be confirmed probably due to non-specific binding or hindered passage through the membrane of the organelle. The work presented describes a novel approach with potential to improve the efficacy of radiopharmaceuticals by enhancing the intracellular retention of radioactivity.

Graphical abstract: Dual-targeting conjugates designed to improve the efficacy of radiolabeled peptides

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Publication details

The article was received on 12 Jun 2012, accepted on 01 Aug 2012 and first published on 02 Aug 2012


Article type: Paper
DOI: 10.1039/C2OB26127H
Citation: Org. Biomol. Chem., 2012,10, 7594-7602
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    Dual-targeting conjugates designed to improve the efficacy of radiolabeled peptides

    C. A. Kluba, A. Bauman, I. E. Valverde, S. Vomstein and T. L. Mindt, Org. Biomol. Chem., 2012, 10, 7594
    DOI: 10.1039/C2OB26127H

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