Radiosynthesis and pre-clinical evaluation of [68Ga] labeled antimicrobial peptide fragment GF-17 as a potential infection imaging PET radiotracer

• Published in: Applied radiation and isotopes 2019-07, Vol.149, p.9-21
• Main Authors: Chopra, Shalini, Singh, Baljinder, Koul, Ashwani, Mishra, Anil K., Robu, Stephanie, Kaur, Amritjyot, Ghai, Anchal, Caplash, Neena, Wester, Hans-Jürgen
• Format: Article
• Language: English
• Subjects: [68Ga]DOTA-GF-17; AMP; Animals; Anti-Infective Agents - pharmacology; Female; Gallium Radioisotopes - chemistry; Gallium Radioisotopes - pharmacokinetics; Gallium Radioisotopes - pharmacology; Infection; Infections - diagnostic imaging; Male; Mice; Mice, Inbred BALB C; Peptide Fragments - pharmacology; PET imaging; Positron-Emission Tomography; Preclinical evaluation; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Tissue Distribution
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2019.04.008

The antimicrobial peptide fragment GF-17 was synthesized in-house and conjugated with DOTA and measured molecular mass of DOTA-GF-17 conjugate was 2489 Da. The peptide conjugate was purified and labeled with [68Ga]. The best radiolabeling efficiency (95.0%) of [68Ga]DOTA-GF-17 was achieved at pH 4 with peptide conjugate amount of 20.0 nmol with 30 min of heating at 95 °C. The product remained stable for up to 3 h. The plasma protein binding and lipophilicity for [68Ga]DOTA-GF-17 were 80.98% and −3.12 respectively. The uptake studies with [68Ga]DOTA- GF-17 in S.aureus and P.aeruginosa bacterial strains demonstrated binding of 69.08% and 43.69% respectively. The animal bio-distribution and PET imaging studies were in agreement showing similar pattern for organs’ tracer distribution and renal excretion. The tracer had rapid blood clearance and uptake in bone marrow and muscles was very low. The highest uptake of [68Ga]DOTA-GF-17 was observed at 45 min and 120 min in S.aureus and P.aeruginosa infections respectively. [68Ga]DOTA-GF-17 could be a promising PET tracer and holds a great scope for taking the product further to perform extensive PET studies in animal infection (using gram negative/positive strains) models to prove the diagnostic utility of this novel PET tracer for futuristic clinical applications. •Antimicrobial peptide fragment GF-17 was synthesized in-house and conjugated with DOTA and characterization of the peptide-conjugate was carried out.•The peptide conjugate was radiolabeled successfully with [68Ga] achieving radiolabeling efficiency of 95.0% using the optimized peptide conjugate amount of 20.0 nmol.•The uptake studies demonstrated that [68Ga]DOTA-peptide had significant binding in the two bacterial strains studied.•The animal bio-distribution and PET imaging studies demonstrated renal mode of excretion for [68Ga]DOTA-GF-17.•The biodistribution studies in infection and inflammation models had shown significant upake of radiolabeled peptide conjugate at the infection sites.•[68Ga]DOTA-GF-17 peptide holds good potential for further undertaking the tracer for detailed pre-clinical evaluation to assess its translational relevance.