Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 5;5(41):26297-26306.
doi: 10.1021/acsomega.0c03601. eCollection 2020 Oct 20.

Microenvironment Stimulated Bioresponsive Small Molecule Carriers for Radiopharmaceuticals

Shubhra Chaturvedi  1 , Puja Panwar Hazari  1 , Ankur Kaul  1 , Anju  1 , Anil K Mishra  1
Affiliations
Review

Microenvironment Stimulated Bioresponsive Small Molecule Carriers for Radiopharmaceuticals

Shubhra Chaturvedi et al. ACS Omega. .

Abstract

The widespread and successful use of radiopharmaceuticals in diagnosis, treatment, and therapeutic monitoring of cancer and other ailments has spawned significant literature. The transition from untargeted to targeted radiopharmaceuticals reflects the various stages of design and development. Targeted radiopharmaceuticals bind to specific biomarkers, get fixed, and highlight the disease site. A new subset of radioprobes, the bioresponsive radiopharmaceuticals, has been developed in recent years. These probes generally benefit from signal enhancement after undergoing molecular changes due to the fluctuations in the environment (pH, redox, or enzymatic activity) at the site of interest. This review presents a comprehensive overview of bioresponsive radioimaging probes covering the basis, application, and scope of development.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Summarization of pH-responsive radioprobes.
Figure 2
Figure 2
Examples of PET-MR dual probes.
Figure 3
Figure 3
Summarization of ROS-responsive probes.
Figure 4
Figure 4
Mechanism of nitroimidazole derivatives to sense hypoxia and intracellular trapping. In a normoxic cell shown as blue, the nitroimidazole does not undergo one-electron reduction. After going through a one-electron reduction in a hypoxic cell, the molecule gets trapped due to interaction with biomacromolecules.
Figure 5
Figure 5
18F-labeled nitroimidazole derivatives as hypoxia-responsive radioprobes.
Figure 6
Figure 6
Examples of the metallic radiopharmaceutical for hypoxia imaging.
Figure 7
Figure 7
Mechanism of Cu-ATSM to sense hypoxia and intracellular trapping.
Figure 8
Figure 8
Chelate scaffold for copper in hypoxia sensing.
Figure 9
Figure 9
Examples of enzyme-responsive PET/SPECT probes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. van Duijnhoven S. M.; Robillard M. S.; Langereis S.; Grüll H. Bioresponsive probes for molecular imaging: concepts and in vivo applications. Contrast Media Mol. Imaging 2015, 10 (4), 282–308. 10.1002/cmmi.1636. - DOI - PubMed
    2. Chaturvedi S.; Kaul A.; Hazari P. P.; Mishra A. K. Mapping neuroreceptors with metal-labeled radiopharmaceuticals. MedChemComm 2017, 8 (5), 855–870. 10.1039/C6MD00610H. - DOI - PMC - PubMed
    3. Chaturvedi S.; Mishra A. K. Small molecule radiopharmaceuticals–a review of current approaches. Front. Med. 2016, 3, 5.10.3389/fmed.2016.00005. - DOI - PMC - PubMed
    1. Cho M. H.; Shin S. H.; Park S. H.; Kadayakkara D. K.; Kim D.; Choi Y. Targeted, Stimuli-Responsive, and Theranostic 19F Magnetic Resonance Imaging Probes. Bioconjugate Chem. 2019, 30 (10), 2502–2518. 10.1021/acs.bioconjchem.9b00582. - DOI - PubMed
    2. Pinto S. M.; Tomé V.; Calvete M. J.; Castro M. M. C.; Tóth É.; Geraldes C. F. Metal-based redox-responsive MRI contrast agents. Coord. Chem. Rev. 2019, 390, 1–31. 10.1016/j.ccr.2019.03.014. - DOI
    1. Apte S.; Chin F. T.; Graves E. E. Molecular imaging of hypoxia: strategies for probe design and application. Curr. Org. Synth. 2011, 8 (4), 593–603. and references therein10.2174/157017911796117179. - DOI - PMC - PubMed
    1. Hunt J. F.; Rath P.; Rothschild K. J.; Engelman D. M. Spontaneous, pH-dependent membrane insertion of a transbilayer α-helix. Biochemistry 1997, 36 (49), 15177–15192. 10.1021/bi970147b. - DOI - PubMed
    2. Va̅vere A. L.; Biddlecombe G. B.; Spees W. M.; Garbow J. R.; Wijesinghe D.; Andreev O. A.; Engelman D. M.; Reshetnyak Y. K.; Lewis J. S. A novel technology for the imaging of acidic prostate tumors by positron emission tomography. Cancer Res. 2009, 69 (10), 4510–4516. 10.1158/0008-5472.CAN-08-3781. - DOI - PMC - PubMed
    3. Viola-Villegas N. T.; Carlin S. D.; Ackerstaff E.; Sevak K. K.; Divilov V.; Serganova I.; Kruchevsky N.; Anderson M.; Blasberg R. G.; Andreev O. A.; Engelman D. M.; Koutcher J. A.; Reshetnyak Y. K.; Lewis J. S. Understanding the pharmacological properties of a metabolic PET tracer in prostate cancer. Proc. Natl. Acad. Sci. U. S. A. 2014, 111 (20), 7254–7259. 10.1073/pnas.1405240111. - DOI - PMC - PubMed
    4. Demoin D. W.; Wyatt L. C.; Edwards K. J.; Abdel-Atti D.; Sarparanta M.; Pourat J.; Longo V. A.; Carlin S. D.; Engelman D. M.; Andreev O. A.; Reshetnyak Y. K.; Viola-Villegas N.; Lewis J. S. PET imaging of extracellular pH in tumors with 64Cu-and 18F-labeled pHLIP peptides: a structure–activity optimization study. Bioconjugate Chem. 2016, 27 (9), 2014–2023. 10.1021/acs.bioconjchem.6b00306. - DOI - PMC - PubMed
    5. Macholl S.; Morrison M. S.; Iveson P.; Arbo B. E.; Andreev O. A.; Reshetnyak Y. K.; Engelman D. M.; Johannesen E. In vivo pH imaging with 99m Tc-pHLIP. Mol. Imaging Biol. 2012, 14 (6), 725–734. 10.1007/s11307-012-0549-z. - DOI - PMC - PubMed
    6. Daumar P.; Wanger-Baumann C. A.; Pillarsetty N.; Fabrizio L.; Carlin S. D.; Andreev O. A.; Reshetnyak Y. K.; Lewis J. S. Efficient 18F-labeling of large 37-amino-acid pHLIP peptide analogues and their biological evaluation. Bioconjugate Chem. 2012, 23 (8), 1557–1566. 10.1021/bc3000222. - DOI - PMC - PubMed
    7. Flavell R. R.; Truillet C.; Regan M. K.; Ganguly T.; Blecha J. E.; Kurhanewicz J.; VanBrocklin H. F.; Keshari K. R.; Chang C. J.; Evans M. J.; Wilson D. M. Caged [18F] FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography. Bioconjugate Chem. 2016, 27 (1), 170–178. 10.1021/acs.bioconjchem.5b00584. - DOI - PMC - PubMed
    1. Vologdin N.; Rolla G. A.; Botta M.; Tei L. Orthogonal synthesis of a heterodimeric ligand for the development of the Gd III–Ga III ditopic complex as a potential pH-sensitive MRI/PET probe. Org. Biomol. Chem. 2013, 11 (10), 1683–1690. 10.1039/c2ob27200h. - DOI - PubMed
    2. Frullano L.; Catana C.; Benner T.; Sherry A. D.; Caravan P. Bimodal MR–PET agent for quantitative pH imaging. Angew. Chem., Int. Ed. 2010, 49 (13), 2382–2384. 10.1002/anie.201000075. - DOI - PMC - PubMed