An improved synthesis of n-(4-[18 f]fluorobenzoyl)-interleukin-2 for the preclinical pet imaging of tumour-infiltrating t-cells in ct26 and mc38 colon cancer models

Abstract

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[18 F]fluorobenzoyl)-interleukin-2 ([18 F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [18 F]FB-IL-2, which reduces synthesis time and improves radiochem-ical yield. With this optimized approach, [18 F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [18 F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [18 F]FB-IL-2. Significant improvements in the radiochemical manufacture of [18 F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.