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Apoptosis imaging in oncology by means of positron emission tomography : a review

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Abstract
To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively F-18-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate F-18-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the Tc-99m-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both F-18-ML-10 and F-18-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using F-18-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using F-18-CP18, remains to be proven and warrants further investigation.
Keywords
Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, apoptosis, positron emission tomography, oncology

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MLA
Van De Wiele, Christophe, et al. “Apoptosis Imaging in Oncology by Means of Positron Emission Tomography : A Review.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 22, no. 5, 2021, doi:10.3390/ijms22052753.
APA
Van De Wiele, C., Ustmert, S., De Spiegeleer, B., De Jonghe, P.-J., Sathekge, M., & Alex, M. (2021). Apoptosis imaging in oncology by means of positron emission tomography : a review. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(5). https://doi.org/10.3390/ijms22052753
Chicago author-date
Van De Wiele, Christophe, Sezgin Ustmert, Bart De Spiegeleer, Pieter-Jan De Jonghe, Mike Sathekge, and Maes Alex. 2021. “Apoptosis Imaging in Oncology by Means of Positron Emission Tomography : A Review.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 (5). https://doi.org/10.3390/ijms22052753.
Chicago author-date (all authors)
Van De Wiele, Christophe, Sezgin Ustmert, Bart De Spiegeleer, Pieter-Jan De Jonghe, Mike Sathekge, and Maes Alex. 2021. “Apoptosis Imaging in Oncology by Means of Positron Emission Tomography : A Review.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 (5). doi:10.3390/ijms22052753.
Vancouver
1.
Van De Wiele C, Ustmert S, De Spiegeleer B, De Jonghe P-J, Sathekge M, Alex M. Apoptosis imaging in oncology by means of positron emission tomography : a review. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2021;22(5).
IEEE
[1]
C. Van De Wiele, S. Ustmert, B. De Spiegeleer, P.-J. De Jonghe, M. Sathekge, and M. Alex, “Apoptosis imaging in oncology by means of positron emission tomography : a review,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 22, no. 5, 2021.
@article{8720203,
  abstract     = {{To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively F-18-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate F-18-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the Tc-99m-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both F-18-ML-10 and F-18-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using F-18-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using F-18-CP18, remains to be proven and warrants further investigation.}},
  articleno    = {{2753}},
  author       = {{Van De Wiele, Christophe and Ustmert, Sezgin and De Spiegeleer, Bart and De Jonghe, Pieter-Jan and Sathekge, Mike and Alex, Maes}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis,apoptosis,positron emission tomography,oncology}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{14}},
  title        = {{Apoptosis imaging in oncology by means of positron emission tomography : a review}},
  url          = {{http://dx.doi.org/10.3390/ijms22052753}},
  volume       = {{22}},
  year         = {{2021}},
}

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