An Improved Synthesis of N-(4-[<sup>18</sup>F]Fluorobenzoyl)-Interleukin-2 for the Preclinical PET Imaging of Tumour-Infiltrating T-cells in CT26 and MC38 Colon Cancer Models

oleh: Shivashankar Khanapur, Fui Fong Yong, Siddesh V. Hartimath, Lingfan Jiang, Boominathan Ramasamy, Peter Cheng, Pradeep Narayanaswamy, Julian L. Goggi, Edward George Robins

Format: Article
Diterbitkan: MDPI AG 2021-03-01

Deskripsi

Positron emission tomography (PET) imaging of activated T-cells with <i>N</i>-(4-[<sup>18</sup>F]fluorobenzoyl)-interleukin-2 ([<sup>18</sup>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 [<sup>18</sup>F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [<sup>18</sup>F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [<sup>18</sup>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 [<sup>18</sup>F]FB-IL-2. Significant improvements in the radiochemical manufacture of [<sup>18</sup>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.