Abstract
Positron emission tomography (PET) imaging of activated T-cells with N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]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 [18F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [18F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [18F]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 [18F]FB-IL-2. Significant improvements in the radiochemical manufacture of [18F]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.
Highlights
We have adapted the four-step, two-pot procedure to synthesize [18 F]FB-IL-2 from those previously reported with several modifications as shown in Scheme 1 [5,7,10,11]
Crude [18 F]SFB was synthesised via three-step reactions (Scheme 1) using a Scintomics GRPTM module
Reduce the total synthesis time by ~30 min compared to previously developed methods (i.e., 1.0 ± 0.4% radiochemical yields (RCYs))
Summary
Immune responses are commonly assessed by measuring lymphocytes in whole blood and/or by biopsies of tumour, spleen and lymph nodes. These methods are invasive and do not provide spatiotemporal information about the dynamic immune responses to these therapies in heterogeneous tumour microenvironments. In this context, non-invasive positron emission tomography (PET) imaging of immune cells, especially T cells, might aid in patient selection, response prediction and treatment evaluation following immunotherapeutic intervention [1]
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