[PMID]: | 28255355 |
[Au] Autor: | Buckle T; van der Wal S; van Malderen SJ; Müller L; Kuil J; van Unen V; Peters RJ; van Bemmel ME; McDonnell LA; Velders AH; Koning F; Vanhaeke F; van Leeuwen FW |
[Ad] Endereço: | Interventional Molecular Imaging laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands;; Division of Molecular Pathology, Netherlands Cancer Institute- Antoni van Leeuwenhoek hospital (NKI-AvL), Amsterdam, the Netherlands. |
[Ti] Título: | Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics. |
[So] Source: | Theranostics;7(3):624-633, 2017. |
[Is] ISSN: | 1838-7640 |
[Cp] País de publicação: | Australia |
[La] Idioma: | eng |
[Ab] Resumo: | 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 and 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 and 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 or In) 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-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), 3) compare biodistribution patterns obtained with ICP-MS ( Ho) and radiodetection ( In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging ( Ho) 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. LA-ICP-MS imaging ( Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the intracellular distribution. biodistribution patterns obtained with ICP-MS ( Ho) and radiodetection ( In) 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. |
[Mh] Termos MeSH primário: |
Espectrometria de Massas/métodos Imagem Multimodal/métodos Patologia Molecular/métodos Receptores CXCR4/análise Nanomedicina Teranóstica/métodos
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[Mh] Termos MeSH secundário: |
Animais Carbocianinas/administração & dosagem Citometria de Fluxo Corantes Fluorescentes/administração & dosagem Camundongos Ácido Pentético/administração & dosagem Radioisótopos/administração & dosagem
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (CXCR4 protein, mouse); 0 (Carbocyanines); 0 (Fluorescent Dyes); 0 (Radioisotopes); 0 (Receptors, CXCR4); 0 (cyanine dye 5); 7A314HQM0I (Pentetic Acid) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171023 |
[Lr] Data última revisão:
| 171023 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170304 |
[St] Status: | MEDLINE |
[do] DOI: | 10.7150/thno.17484 |
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