Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab
Radiopharmaceuticals can be used for targetspecific functional diagnostics, such as PET or SPECT imaging, or radionuclide therapy of diseased tissue, depending on the incorporated radionuclide. Following initial in vitro testing, radiopharmaceutical candidates are usually further characterized in sm...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2022-09-01
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| Series: | Current Directions in Biomedical Engineering |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/cdbme-2022-1136 |
| _version_ | 1797947882714693632 |
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| author | Sihver Wiebke Nitt-Weber Anne-Kathrin Behrens Stephan Ullrich Martin Pietzsch Hans-Jürgen Namazian Jam Negin Schmieder Florian Sonntag Frank |
| author_facet | Sihver Wiebke Nitt-Weber Anne-Kathrin Behrens Stephan Ullrich Martin Pietzsch Hans-Jürgen Namazian Jam Negin Schmieder Florian Sonntag Frank |
| author_sort | Sihver Wiebke |
| collection | DOAJ |
| description | Radiopharmaceuticals can be used for targetspecific functional diagnostics, such as PET or SPECT imaging, or radionuclide therapy of diseased tissue, depending on the incorporated radionuclide. Following initial in vitro testing, radiopharmaceutical candidates are usually further characterized in small animals. Since reduction, replacement and refinement (3R) of animal testing is a central precept in preclinical research it would be beneficial to replace at least some of these tests by alternative methods. Using micro physiological system technology, various organ-on-chip models can be created with human cell systems/organoids, which are operated in a circulatory system under defined physiological conditions. Here we present first attempts to introduce micro physiological systems for evaluating radiopharmaceuticals using the radiolabeled anti-EGFR antibody cetuximab as reference compound. In a micro physiological system equipped with six 96-well plate-like microwells in a flow chamber, binding of 64Cu and 68Ga-labeled cetuximab to cells and spheroids grown from A431 (EGFR-positive) and MDA-MB435S (EGFR-negative) cells was measured and compared to conventional microplates. Specific saturation binding of radiolabeled cetuximab at increasing concentrations was analyzed using a phosphor imaging system. The affinity of radiolabeled cetuximab towards A431 spheroids measured in the micro physiological system was in the same range as that of the spheroids in conventional microplates. Within the assays in micro physiological systems, the results showed a trend towards increased affinity for A431 monolayers compared to the spheroids. The values of binding capacity for radiolabeled cetuximab on 2D and 3D A431 cell culture models were in the same order of magnitude when measured in micro physiological systems or in microplates. Building on these first promising results, the work will continue on MPS modules containing advanced human spheroid/ organoid models. |
| first_indexed | 2024-04-10T21:33:37Z |
| format | Article |
| id | doaj.art-4dbc84133e704efe83c9863db0b255d3 |
| institution | Directory Open Access Journal |
| issn | 2364-5504 |
| language | English |
| last_indexed | 2024-04-10T21:33:37Z |
| publishDate | 2022-09-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Current Directions in Biomedical Engineering |
| spelling | doaj.art-4dbc84133e704efe83c9863db0b255d32023-01-19T12:47:03ZengDe GruyterCurrent Directions in Biomedical Engineering2364-55042022-09-018253253510.1515/cdbme-2022-1136Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximabSihver Wiebke0Nitt-Weber Anne-Kathrin1Behrens Stephan2Ullrich Martin3Pietzsch Hans-Jürgen4Namazian Jam Negin5Schmieder Florian6Sonntag Frank7Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research,Dresden, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research,Dresden, GermanyFraunhofer Institute for Material and Beam Technology IWS,Dresden, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research,Dresden, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research,Dresden, GermanyFraunhofer Institute for Material and Beam Technology IWS,Dresden, GermanyFraunhofer Institute for Material and Beam Technology IWS,Dresden, GermanyFraunhofer Institute for Material and Beam Technology IWS,Dresden, GermanyRadiopharmaceuticals can be used for targetspecific functional diagnostics, such as PET or SPECT imaging, or radionuclide therapy of diseased tissue, depending on the incorporated radionuclide. Following initial in vitro testing, radiopharmaceutical candidates are usually further characterized in small animals. Since reduction, replacement and refinement (3R) of animal testing is a central precept in preclinical research it would be beneficial to replace at least some of these tests by alternative methods. Using micro physiological system technology, various organ-on-chip models can be created with human cell systems/organoids, which are operated in a circulatory system under defined physiological conditions. Here we present first attempts to introduce micro physiological systems for evaluating radiopharmaceuticals using the radiolabeled anti-EGFR antibody cetuximab as reference compound. In a micro physiological system equipped with six 96-well plate-like microwells in a flow chamber, binding of 64Cu and 68Ga-labeled cetuximab to cells and spheroids grown from A431 (EGFR-positive) and MDA-MB435S (EGFR-negative) cells was measured and compared to conventional microplates. Specific saturation binding of radiolabeled cetuximab at increasing concentrations was analyzed using a phosphor imaging system. The affinity of radiolabeled cetuximab towards A431 spheroids measured in the micro physiological system was in the same range as that of the spheroids in conventional microplates. Within the assays in micro physiological systems, the results showed a trend towards increased affinity for A431 monolayers compared to the spheroids. The values of binding capacity for radiolabeled cetuximab on 2D and 3D A431 cell culture models were in the same order of magnitude when measured in micro physiological systems or in microplates. Building on these first promising results, the work will continue on MPS modules containing advanced human spheroid/ organoid models.https://doi.org/10.1515/cdbme-2022-1136radiopharmaceuticalsmicro physiological systemsradiopharmacological parameterspreclinical trialsreduction experimental animals |
| spellingShingle | Sihver Wiebke Nitt-Weber Anne-Kathrin Behrens Stephan Ullrich Martin Pietzsch Hans-Jürgen Namazian Jam Negin Schmieder Florian Sonntag Frank Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab Current Directions in Biomedical Engineering radiopharmaceuticals micro physiological systems radiopharmacological parameters preclinical trials reduction experimental animals |
| title | Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab |
| title_full | Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab |
| title_fullStr | Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab |
| title_full_unstemmed | Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab |
| title_short | Introducing micro physiological systems to evaluate new radiopharmaceuticals: A binding study with radiolabeled cetuximab |
| title_sort | introducing micro physiological systems to evaluate new radiopharmaceuticals a binding study with radiolabeled cetuximab |
| topic | radiopharmaceuticals micro physiological systems radiopharmacological parameters preclinical trials reduction experimental animals |
| url | https://doi.org/10.1515/cdbme-2022-1136 |
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