RT Journal Article SR Electronic T1 Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 308 OP 314 DO 10.2967/jnumed.113.128397 VO 55 IS 2 A1 Thomas Ebenhan A1 Jan Rijn Zeevaart A1 Jacobus D. Venter A1 Thavendran Govender A1 Gert H. Kruger A1 Neil V. Jarvis A1 Mike M. Sathekge YR 2014 UL http://jnm.snmjournals.org/content/55/2/308.abstract AB 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 oil-induced 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-NOTA-UBI29-41 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.