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Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes

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Abstract

Purpose

Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.

Procedures

Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters.

Results

The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide.

Conclusions

Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.

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Acknowledgments

This work was supported by the National Institute of General Medical Sciences Grant RO1 GM073857 to OAA and YKR.

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Authors and Affiliations

  1. Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA

    Ramona-Cosmina Adochite, Anna Moshnikova, Jovana Golijanin, Oleg A. Andreev & Yana K. Reshetnyak

  2. Department of Computer Sciences and Statistics, University of Rhode Island, 9 Greenhouse Road, Kingston, RI, 02881, USA

    Natallia V. Katenka

Authors
  1. Ramona-Cosmina Adochite
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  2. Anna Moshnikova
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  3. Jovana Golijanin
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  4. Oleg A. Andreev
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  5. Natallia V. Katenka
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  6. Yana K. Reshetnyak
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Corresponding author

Correspondence to Yana K. Reshetnyak.

Ethics declarations

All animal studies were conducted according to the animal protocol AN04-12-011 approved by the Institutional Animal Care and Use Committee at the University of Rhode Island, in compliance with the principles and procedures outlined by NIH for the Care and Use of Animals.

Conflict of Interest

Andreev and Reshetnyak own stocks in company pHLIP, Inc. They have disclosed those interestsfully to the University of Rhode Island, and have in place an approved plan for managing any potentialconflicts. The following authors, Adochite, Moshnikova, Golijanin, and Katenka, declare no conflict of interest.

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Adochite, RC., Moshnikova, A., Golijanin, J. et al. Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes. Mol Imaging Biol 18, 686–696 (2016). https://doi.org/10.1007/s11307-016-0949-6

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  • DOI: https://doi.org/10.1007/s11307-016-0949-6

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