Preclinical Evaluation of sigma up 68 Gamma a-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. sigma up 99m theta c-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 sigma up 68 Gamma a, and investigated in a rabbit infection model. sigma up 68 Gamma a was obtained from a 1.85-GBq 68Ge/ sigma up 68 Gamma a generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. sigma up 68 Gamma a-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ( sigma up 68 Gamma a-NOTA-UBI29-41) was formulated in saline solution, and 101 plus or minus 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. 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 sigma up 68 Gamma a-NOTA-UBI29-41 peaked at 3.8 plus or minus 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 plus or minus 5.2 %ID was recovered in total urine. sigma up 68 Gamma a-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 plus or minus 0.93, 2.9 plus or minus 0.50, 3.5 plus or minus 0.86, and 3.8 plus or minus 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. sigma up 68 Gamma a-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