Evaluation of a Labelled Bacteriophage with 99mTc as a Potential Agent for Infection Diagnosis. 2016

María Elena Cardoso, and Leticia Fernández, and Emilia Tejería, and Patricia Esperón, and Mariella Terán

OBJECTIVE The design of target-specific molecular imaging probes to determine infection sites are mainly based on the biochemistry of the inflammatory response that may lead to an ideal agent for infection imaging. Infectious diseases timely and specifically diagnosed can be clinically challenging but essential for the patient's recovery. Laboratory tests can detect the responsible microorganism but cannot discriminate between sterile inflammatory disease and truly infectious disease. On the other hand, scintigraphic images, can pinpoint the infection in the body. METHODS Bacteriophages (phages) are viruses that infect specific bacterial strains. Given the composition of the protein capsid, they could be used as radiopharmaceuticals to diagnose bacterial infection. In this case, PP7 phage was labelled and evaluated as a specific tracer for Pseudomonas aeruginosa infections. 99mTc-Phage synthesis used HYNIC as a bifunctional agent. Physicochemical evaluation included studies such as stability in time, ligand exchange, lipophilicity and bacterial binding assay. Three groups of animals namely; healthy, infected with Pseudomonas aeruginosa and induced sterile inflammation were used to conduct biological evaluation Results: The radiolabelling process required size exclusion purification of the 99mTc-Phage, which was obtained with a radiochemical purity higher than 90%, during 18 hours post labelling. The collective accumulation in the stomach, small intestine and large intestine and thyroid of 99mTc-Phage was negligible, indicating no in vivo reoxidation. The complex presented urinary elimination. Target/ non-target ratio (T/NT) was determined both for sterile inflammation and for infection. Values were 2.5 ± 0.4 and 4.2 ± 0.3 respectively. These values indicate significant differences between sterile inflammation and infection by Pseudomonas aeruginosa (p<0.05 unpaired two sided t-test). CONCLUSIONS Targeted biodistribution profile and good T/NT ratios, indicate that this complex presents enough specificity to discriminate between infection caused by Pseudomonas aeruginosa and sterile inflammation.

UI MeSH Term Description Entries
D011552 Pseudomonas Infections Infections with bacteria of the genus PSEUDOMONAS. Infections, Pseudomonas,Pseudomonas aeruginosa Infection,Infection, Pseudomonas,Pseudomonas Infection,Pseudomonas aeruginosa Infections
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001435 Bacteriophages Viruses whose hosts are bacterial cells. Phages,Bacteriophage,Phage
D013667 Technetium The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, and atomic number 43. All technetium isotopes are radioactive. Technetium 99m (m Technetium 99m,99m, Technetium
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019275 Radiopharmaceuticals Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161) Radiopharmaceutical

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