Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker

• Published in: Scientific reports Vol. 12; no. 1; pp. 18584 - 11
• Main Authors: Kumar, Pardeep, Thakur, Riptee, Acharya, Pratap Chandra, Mohan, Hosahalli K., Pallavi, U. N., Maheshwari, Divya, Mohammed K M, Afsal, Kumar, Aishwarya, Goud Nerella, Sridhar, Joshi, Raman Kumar, Kumar, Manoj, Nagaraj, Chandana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-11-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/2321; 692/53/2423; 692/700/139; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; ATP-Binding Cassette Transporters - metabolism; Biodistribution; Breast cancer; Chemoresistance; Computed tomography; Drug Resistance, Neoplasm; Fluorine; Fluorine Radioisotopes - chemistry; Humanities and Social Sciences; Liquid chromatography; Mice; multidisciplinary; NMR; Nuclear magnetic resonance; P-Glycoprotein; Positron emission tomography; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography - methods; Quality control; Radioactive tracers; Radiopharmaceuticals; Science; Science (multidisciplinary); Tissue Distribution
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-22930-6

P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (
18
F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by
1
H-NMR and
13
C-NMR. AVT-011 was labeled with
18
F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [
18
F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [
18
F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.