Noninvasive visualization of tumoral fibrin deposition using a peptidic fibrin-binding single photon emission computed tomography tracer

L.W.E. Starmans, T.R. van Mourik, R. Rossin, I. Verel, K. Nicolay, H. Grüll

    Research output: Contribution to journalArticleAcademicpeer-review

    9 Citations (Scopus)

    Abstract

    Fibrin deposition plays an important role in the formation of mature tumor stroma and provides a facilitating scaffold for tumor angiogenesis. This study investigates the potential of the 111In-labeled fibrin-binding peptide EPep for SPECT imaging of intratumoral fibrin deposition. 111In-EPep and negative control 111In-NCEPep were synthesized and characterized in vitro. In vivo SPECT images and ex vivo biodistribution profiles and autoradiographs were obtained in a fibrin-rich BT-20 breast cancer mouse model. Furthermore, biodistribution profiles were obtained in the fibrin-poor MDA-MD-231 model. In vitro, 111In-EPep displayed significantly more binding than 111In-NCEPep toward human and mouse derived fibrin. SPECT/CT images displayed a marked SPECT signal in the tumor area for BT-20 tumor bearing mice injected with EPep but not for mice injected with NCEPep. Biodistribution profiles of BT-20 tumor bearing mice 3 h post-tracer injection showed significantly higher tumor uptake for EPep with respect to NCEPep (0.39 ± 0.14 and 0.11 ± 0.03% ID g-1, respectively), whereas uptake in other organs was similar for EPep and NCEPep. Autoradiography of BT-20 tumor sections displayed a high signal for EPep which colocalized with intratumoral fibrin deposits. Histological evaluation of MDA-MB-231 tumor sections displayed no significant tumor stroma and only minute fibrin deposits. Biodistribution profiles in MDA-MB-231 tumor bearing mice 3 h post-injection showed EPep tumor uptake (0.14 ± 0.04% ID g-1) which was significantly lower with respect to EPep BT-20 tumor uptake, indicating fibrin-specificity of EPep tumoral uptake. In conclusion, this work demonstrates the potential of EPep SPECT imaging for visualization of tumoral fibrin deposition.

    Original languageEnglish
    Pages (from-to)1921-1928
    Number of pages8
    JournalMolecular Pharmaceutics
    Volume12
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2015

    Keywords

    • cancer
    • fibrin
    • fibrin-binding peptide
    • single photon emission computed tomography (SPECT)
    • tumor stroma

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