Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics
| Autor: | Stijn Van Malderen, Joeri Kuil, Frits Koning, Vincent van Unen, Ruud J. B. Peters, Fijs W. B. van Leeuwen, Margaretha E. M. van Bemmel, Larissa Müller, Tessa Buckle, Liam A. McDonnell, Steffen van der Wal, Frank Vanhaeke, Aldrik H. Velders |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Fluorescence-lifetime imaging microscopy Medicine (miscellaneous) CHEMOKINE RECEPTOR CXCR4 Multimodal Imaging THERAPY Theranostic Nanomedicine Mice BU Contaminants & Toxins DESIGN molecular pathology Fluorescence microscope Medicine and Health Sciences Pathology Molecular Pharmacology Toxicology and Pharmaceutics (miscellaneous) Inductively coupled plasma mass spectrometry mass spectrometry LA-ICP-MS imaging medicine.diagnostic_test Chemistry Carbocyanines Pentetic Acid Flow Cytometry Fluorescence 3. Good health Bimodal SPECT Mass cytometry fluorescence Research Paper EXPRESSION mass cytometry Receptors CXCR4 TISSUES BU Contaminanten & Toxines Molecular imaging bimodal Flow cytometry 03 medical and health sciences In vivo CYTOMETRY MULTIPLE-MYELOMA medicine Animals BREAST-CANCER BioNanoTechnology Fluorescent Dyes VLAG Molecular pathology Radioisotopes radioisotopes Mass spectrometry BIOASSAYS POLYMER molecular imaging Molecular biology 030104 developmental biology Biophysics |
| Zdroj: | Theranostics, 7(3), 624-633 Theranostics 7 (2017) 3 THERANOSTICS Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either Ho-165 or In-111) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (Ho-165-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (Ho-165), 3) compare in vivo biodistribution patterns obtained with ICP-MS (Ho-165) and radiodetection (In-111) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (Ho-165) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 +/- 141 nM and 245 +/- 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (Ho-165) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the intracellular distribution. In vivo biodistribution patterns obtained with ICP-MS (Ho-165) and radiodetection (In-111) of the hybrid peptide were shown to be similar. Assessment of tracer distribution in excised tissues revealed the location of tracer uptake with both LA-ICP-MS-imaging and fluorescence imaging. Conclusion: Lanthanide-isotope chelation expands the scope of fluorescent/ radioactive hybrid tracers to include MS-based analytical tools such as mass-cytometry, ICP-MS and LA-ICP-MS imaging in molecular pathology. In contradiction to common expectations, MS detection using a single chelate imaging agent was shown to be feasible, enabling a direct link between nuclear medicine-based imaging and theranostic methods. |
| Databáze: | OpenAIRE |
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