Molecular Imaging of Cancer Using X-ray Computed Tomography with Protease Targeted Iodinated Activity-Based Probes

Hanmant K. Gaikwad, Darya Tsvirkun, Yael Ben-Nun, Emmanuelle Merquiol, Rachela Popovtzer, Galia Blum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


X-ray computed tomography (CT) is a robust, precise, fast, and reliable imaging method that enables excellent spatial resolution and quantification of contrast agents throughout the body. However, CT is largely inadequate for molecular imaging applications due mainly to its low contrast sensitivity that forces the use of large concentrations of contrast agents for detection. To overcome this limitation, we generated a new class of iodinated nanoscale activity-based probes (IN-ABPs) that sufficiently accumulates at the target site by covalently binding cysteine cathepsins that are exceptionally highly expressed in cancer. The IN-ABPs are comprised of a short targeting peptide selective to specific cathepsins, an electrophilic moiety that allows activity-dependent covalent binding, and tags containing dendrimers with up to 48 iodine atoms. IN-ABPs selectively bind and inhibit activity of recombinant and intracellular cathepsin B, L, and S. We compared the in vivo kinetics, biodistribution, and tumor accumulation of IN-ABPs bearing 18 and 48 iodine atoms each, and their control counterparts lacking the targeting moiety. Here we show that although both IN-ABPs bind specifically to cathepsins within the tumor and produce detectable CT contrast, the 48-iodine bearing IN-ABP was found to be optimal with signals over 2.1-fold higher than its nontargeted counterpart. In conclusion, this study shows the synthetic feasibility and potential utility of IN-ABPs as potent contrast agents that enable molecular imaging of tumors using CT.

Original languageAmerican English
Pages (from-to)1582-1591
Number of pages10
JournalNano Letters
Issue number3
StatePublished - 14 Mar 2018

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.


  • Cathepsins
  • computed tomography
  • iodine contrast agent
  • molecular imaging
  • nanoscale activity-based probes


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