[18F]RPS-544: A PET tracer for imaging the chemokine receptor CXCR4

• Published in: Nuclear medicine and biology 2018-05, Vol.60, p.37-44
• Main Authors: Amor-Coarasa, Alejandro, Kelly, James, Ponnala, Shashikanth, Vedvyas, Yogindra, Nikolopoulou, Anastasia, Williams, Clarence, Jin, Moonsoo M., David Warren, J., Babich, John W.
• Format: Article
• Language: English
• Subjects: Affinity; Blood; Chemokine; Chemokines; CXCR4; Fluorine isotopes; Imaging; Intestine; Lymphocytes; Metastasis; Muscles; Organs; Peptides; PET; Pharmacology; Positron emission; Prognosis; Radioactive tracers; Radiolabelling; Tomography; Tumors; Xenografts; Xenotransplantation
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2018.01.004

CXCR4 specific [18F]-labeled positron emission tomography (PET) imaging agents are needed which would enable general distribution of the radiotracer for clinical investigation. We sought to synthesize, radiolabel and evaluate [18F]RPS-544, a novel non-peptide CXCR4 antagonist as a CXCR4 specific probe. We compared [18F]RPS-544 with the previously published [18F]-3 ([18F]RPS-510 in this paper) in a bi-lateral tumor model of differential CXCR4 expression for its ability to selectively target CXCR4 expression. Radiolabeling of [18F]RPS-544 and [18F]RPS-510 was performed by aromatic substitution on a 6-nitropyridyl group using no-carrier-added [18F]fluoride under basic conditions. 18F incorporation was determined by radioHPLC. Semi-preparative HPLC was used to purify the final product prior to reformulation. Imaging and biodistribution was performed in nude mice with bilateral PC3 (CXCR4+ and WT) xenograft tumors at 1, 2 and 4 h post injection. RPS-544 bound CXCR4 with an IC50 of 4.9 ± 0.3 nM. [18F]RPS-544 showed preferential uptake in CXCR4+ tumors, with a CXCR4/WT ratio of 3.3 ± 1.3 at 1 h p.i. and 2.3 ± 0.5 at 2 h p.i. Maximum uptake in the CXCR4+ tumors was 3.4 ± 1.2%ID/g at 1 h p.i., significantly greater (p = 0.003) than the uptake in the WT tumor. Tumor/blood ratios were 2.5 ± 0.4 and 3.6 ± 0.3 at 1 and 2 h p.i. Tumor/muscle ratios were >4 at all time-points. Tumor/lung ratios were >2 at 1 h and 2 h p.i. Substantial uptake was observed in the liver (15–25%ID/g), kidneys (25–35%ID/g), the small intestine (1–7%ID/g) and the large intestine (1–12%ID/g). Blood concentrations varied over time (0.5–2%ID/g). All other organs showed uptake of 185 GBq/μmol) achieved during radiosynthesis could lead to accelerated