Biodistribution PET/CT study of hemoglobin-DFO-89Zr complex in healthy and lung tumor-bearing mice
| Autor: | Kiraga, Cerutti, Braniewska, Strzemecki, Sas, Boffi, Savino, Montemiglio, L.C., Turnham, Seaton, Bonamore, Clarkson, Dabkowski, Paisey, S.J., Taciak, Kucharzewska, Rygiel, T.P., Król, M |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
tumor Biodistribution eimide-deferoxamine PET/CT Zr b Hemoglobin immune cells maleimide-deferoxamine protein drug carrier 89Zr Spleen 02 engineering and technology Pharmacology Catalysis lcsh:Chemistry Inorganic Chemistry 03 medical and health sciences Immune system medicine ma Physical and Theoretical Chemistry biodistribution lcsh:QH301-705.5 Molecular Biology Spectroscopy Lung Chemistry Organic Chemistry Oxygen transport General Medicine hemoglobin 021001 nanoscience & nanotechnology 89zr 3. Good health Computer Science Applications 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 Drug delivery 0210 nano-technology Drug carrier |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 4991, p 4991 (2020) International Journal of Molecular Sciences Volume 21 Issue 14 International journal of molecular sciences 21 (2020): 4990–5006. doi:10.3390/ijms21144991 info:cnr-pdr/source/autori:Kiraga,L., Cerutti,G., Braniewska,A., Strzemecki,D., Sas,Z., Boffi,A., Savino,C., Montemiglio,L.C., Turnham,D., Seaton,G., Bonamore,A., Clarkson,R., Dabkowski,A., Paisey,S.J., Taciak,B., Kucharzewska,P., Rygiel,T.P., Król,M/titolo:Biodistribution PET%2FCT study of hemoglobin-DFO-89Zr complex in healthy and lung tumor-bearing mice/doi:10.3390%2Fijms21144991/rivista:International journal of molecular sciences (Print)/anno:2020/pagina_da:4990/pagina_a:5006/intervallo_pagine:4990–5006/volume:21 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21144991 |
| Popis: | Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine &beta 93 is the sole attachment moiety to the &alpha &beta protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naï ve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells. |
| Databáze: | OpenAIRE |
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