Biomaterial Database

Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice. 2020

Łukasz Kiraga, and Gabriele Cerutti, and Agata Braniewska, and Damian Strzemecki, and Zuzanna Sas, and Alberto Boffi, and Carmelinda Savino, and Linda Celeste Montemiglio, and Daniel Turnham, and Gillian Seaton, and Alessandra Bonamore, and Richard Clarkson, and Adam M Dabkowski, and Stephen J Paisey, and Bartłomiej Taciak, and Paulina Kucharzewska, and Tomasz P Rygiel, and Magdalena Król

Department of Cancer Biology, Institute of Biology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.

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 β93 is the sole attachment moiety to the αβ-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 naïve 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.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011868	Radioisotopes	Isotopes that exhibit radioactivity and undergo radioactive decay. (From Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Daughter Isotope,Daughter Nuclide,Radioactive Isotope,Radioactive Isotopes,Radiogenic Isotope,Radioisotope,Radionuclide,Radionuclides,Daughter Nuclides,Daugter Isotopes,Radiogenic Isotopes,Isotope, Daughter,Isotope, Radioactive,Isotope, Radiogenic,Isotopes, Daugter,Isotopes, Radioactive,Isotopes, Radiogenic,Nuclide, Daughter,Nuclides, Daughter
D003676	Deferoxamine	Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.	Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D004337	Drug Carriers	Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.	Drug Carrier
D005260	Female		Females
D006454	Hemoglobins	The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.	Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man