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Monitoring of tumor response to chemotherapy in vivo by a novel small-molecule detector of apoptosis

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Abstract

Utilization of molecular imaging of apoptosis for clinical monitoring of tumor response to anti-cancer treatments in vivo is highly desirable. To address this need, we now present ML-9 (butyl-2-methyl-malonic acid; MW = 173), a rationally designed small-molecule detector of apoptosis, based on a novel alkyl-malonate motif. In proof-of-concept studies, induction of apoptosis in tumor cells by various triggers both in vitro and in vivo was associated with marked uptake of 3H-ML-9 administered in vivo, in correlation with the apoptotic hallmarks of DNA fragmentation, caspase-3 activation and membrane phospholipid scrambling, and with correlative tumor regression. ML-9 uptake following chemotherapy was tumor-specific, with rapid clearance of the tracer from the blood and other non-target organs. Excess of non-labeled “cold” compound competitively blocked ML-9 tumor uptake, thus demonstrating the specificity of ML-9 binding. ML-9 may therefore serve as a platform for a novel class of small-molecule imaging agents for apoptosis, useful for assessment of tumor responsiveness to treatment.

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Acknowledgments

ML-9 is an investigational imaging product developed by Aposende Ltd (formerly NST Ltd.), and all authors receive personal compensation from Aposense.

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Authors and Affiliations

  1. Aposense Ltd., 5 Ha’Odem St., P.O. Box 7119, 49170, Petach-Tiqva, Israel

    Hagit Grimberg, Galit Levin, Anat Shirvan, Avi Cohen, Merav Yogev-Falach, Ayelet Reshef & Ilan Ziv

Authors
  1. Hagit Grimberg
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  2. Galit Levin
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  3. Anat Shirvan
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  4. Avi Cohen
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  5. Merav Yogev-Falach
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  6. Ayelet Reshef
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  7. Ilan Ziv
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Corresponding author

Correspondence to Merav Yogev-Falach.

Additional information

H. Grimberg, G. Levin and A. Shirvan contributed equally to this article.

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Grimberg, H., Levin, G., Shirvan, A. et al. Monitoring of tumor response to chemotherapy in vivo by a novel small-molecule detector of apoptosis. Apoptosis 14, 257–267 (2009). https://doi.org/10.1007/s10495-008-0293-7

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  • DOI: https://doi.org/10.1007/s10495-008-0293-7

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