Ebenhan T., Zeevaart J.R., Venter J.D., Govender T., Kruger G.H., Jarvis N.V., Sathekge M.M.
Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane- 1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging
Department of Nuclear Medicine, University of Pretoria, Steve Biko Academic Hospital, Private Bag X169, Pretoria, 0001, South Africa; School of Chemistry, University of KwaZulu Natal, Durban, South Africa; Research and Development, South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa; Department of Science and Technology, Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa; Medical Research Council of South Africa, Pretoria, South Africa; Unit Catalysis, University of KwaZulu Natal, Durban, South Africa
Ebenhan, T., Department of Nuclear Medicine, University of Pretoria, Steve Biko Academic Hospital, Private Bag X169, Pretoria, 0001, South Africa, School of Chemistry, University of KwaZulu Natal, Durban, South Africa, Research and Development, South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa; Zeevaart, J.R., Department of Science and Technology, Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa; Venter, J.D., Medical Research Council of South Africa, Pretoria, South Africa; Govender, T., Unit Catalysis, University of KwaZulu Natal, Durban, South Africa; Kruger, G.H., School of Chemistry, University of KwaZulu Natal, Durban, South Africa; Jarvis, N.V., Research and Development, South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa; Sathekge, M.M., Department of Nuclear Medicine, University of Pretoria, Steve Biko Academic Hospital, Private Bag X169, Pretoria, 0001, South Africa
Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. 99mTc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane- triacetic acid (NOTA), radiolabeled with 68Ga, and investigated in a rabbit infection model. Methods: 68Ga was obtained from a 1.85-GBq 68Ge/68Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. 68Ga- 1,4,7-triazacyclononane-1,4,7- triacetic-acid-ubiquicidin29-41 (68Ga- NOTA-UBI29-41) was formulated in saline solution, and 101 ± 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oilinduced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue. Results: PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of 68Ga-NOTA-UBI29-41 peaked at 3.8 ± 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 ± 5.2 %ID was recovered in total urine. 68Ga- NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/ inflamed) were 2.9 ± 0.93, 2.9 ± 0.50, 3.5 ± 0.86, and 3.8 ± 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. Conclusion: 68Ga-NOTAUBI29- 41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
gallium 1,4,7 triazacyclononane 1,4,7 triacetic acid ubiquicidin 29 41 ga 68; radioligand; unclassified drug; 1,4,7 triazacyclononane 1,4,7 triacetic acid; 1,4,7-triazacyclononane-N,N',N''-triacetic acid; antimicrobial cationic peptide; diagnostic agent; gallium; heterocyclic compound; radiopharmaceutical agent; ribosomal protein S30; ribosome protein; turpentine; animal experiment; animal model; animal tissue; article; asthma; computer assisted emission tomography; controlled study; drug blood level; drug distribution; drug half life; drug tissue level; drug uptake; drug urine level; isotope labeling; myositis; nonhuman; positron emission tomography; priority journal; rabbit; Staphylococcus infection; 68Ga labeling; animal; chemistry; computer assisted tomography; drug effect; infection; inflammation; lung; metabolism; methodology; PET/CT Imaging; positron emission tomography; scintiscanning; single photon emission computer tomography; Staphylococcus infection; tissue distribution; UBI29-41; ubiquicidin; 68Ga labeling; infection; PET/CT Imaging; UBI29-41; ubiquicidin; Animals; Antimicrobial Cationic Peptides; Gallium Radioisotopes; Heterocyclic Compounds; Infection; Inflammation; Lung; Positron-Emission Tomography; Rabbits; Radiopharmaceuticals; Ribosomal Proteins; Staphylococcal Infections; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Turpentine