New peptide based freeze-dried kit [99mTc-HYNIC]-UBI 29-41 as a human specific infection imaging agent

  Introduction: Ubiquicidin 29-41 (UBI) is a fragment of the cationic antimicrobial peptide that is present in various species including humans. The purpose of this study was to investigate radiochemical and biological characteristics of [6-hydrazinopyridine-3-carboxylic acid (HYNIC)]-UBI 29-41 designed for the labeling with 99mTc using tricine as coligand. Methods: Synthesis was preformed on a solid phase using a standard Fmoc strategy and HYNIC precursor coupled at the N-terminus. Purified peptide conjugate was labeled with 99mTc at 100°C for 10 min. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate stability and affinity to human serum was challenged for 24 hours and its in vitro binding to bacteria was assessed. Biodistribution and accumulation of radiopeptide in staphylococcus aureus infected mice were studied using scintigraphy and ex vivo counting. Results: Radiolabeling was performed at high specific activities, and radiochemical purity was > 95%. The stability of radiolabeled peptide in human serum was excellent. In vitro studies showed 70% of radioactivity was bound to bacteria. After injection into mice with a bacterial infection, removing from the circulation occurred mainly by renal clearance and site of infection was rapidly detected within 30 min. Target to nontarget muscle ratio was 2.099 ± 0.05% at 30 min post injection. Conclusion: [99mTc-HYNIC]-UBI 29-41 showed favorable radiochemical and biological characteristics which permitted detection of the infection with optimal visualization within 30 min.

Keywords:

Antimicrobial peptide , HYNIC , Kit , Ubiquicidin