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

Authors:
Baljinder Singh
Baljinder Singh
Panjab University
Ashwani Koul
Ashwani Koul
Panjab University
India
Anil K Mishra
Anil K Mishra
Institute of Nuclear Medicine and Allied Sciences
Delhi | India
Stephanie Robu
Stephanie Robu
Technische Universität München
Dr. Anchal Ghai, PhD
Dr. Anchal Ghai, PhD
WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
POSTDOCTORAL RESEARCH ASSOCIATE
NUCLEAR MEDICINE, RADIOPHARMACY, MOLECULAR IMAGING, RADIOIMMUNOTHERAPY
ST LOUIS, MISSOURI | United States

Appl Radiat Isot 2019 Jul 10;149:9-21. Epub 2019 Apr 10.

Department of Nuclear Medicine, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

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 [Ga]. The best radiolabeling efficiency (95.0%) of [Ga]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 [Ga]DOTA-GF-17 were 80.98% and -3.12 respectively. The uptake studies with [Ga]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 [Ga]DOTA-GF-17 was observed at 45 min and 120 min in S.aureus and P.aeruginosa infections respectively. [Ga]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.

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http://dx.doi.org/10.1016/j.apradiso.2019.04.008DOI Listing
July 2019
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