PT - JOURNAL ARTICLE AU - Valentina Di Gialleonardo AU - Alberto Signore AU - Andor W.J.M. Glaudemans AU - Rudi A.J.O. Dierckx AU - Erik F.J. De Vries TI - <em>N</em>-(4-<sup>18</sup>F-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes AID - 10.2967/jnumed.111.091306 DP - 2012 May 01 TA - Journal of Nuclear Medicine PG - 679--686 VI - 53 IP - 5 4099 - http://jnm.snmjournals.org/content/53/5/679.short 4100 - http://jnm.snmjournals.org/content/53/5/679.full SO - J Nucl Med2012 May 01; 53 AB - Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the labeling of IL2 with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB) for the synthesis of N-(4-18F-fluorobenzoyl)interleukin-2 (18F-FB-IL2) and the in vitro and in vivo evaluation of this novel radiopharmaceutical for the detection of IL2 receptor–positive cells by PET. Methods: 18F-SFB was efficiently prepared using a 3-step radiochemical pathway. Purified 18F-SFB was incubated with IL2 in borate buffer (pH 8.5) and ethanol at 50°C for 10 min. 18F-FB-IL2 was purified by reversed-phase high-performance liquid chromatography. As in vitro quality controls, a biologic binding assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, mass spectrometry, and 3-chloroacetic acid precipitation stability tests were performed. Biodistribution studies were performed in BALB/c mice to evaluate the distribution of the tracer in healthy animals. PET experiments were performed in severe combined immunodeficiency disease mice inoculated with phytohemoagglutinin-activated human peripheral blood mononuclear cells (hPBMc). Whole-body images were acquired 30 min after injection of 5–15 MBq of 18F-FB-IL2. Results: 18F-SFB was produced with a 34%–38% radiochemical yield. The radiochemical purity after solid-phase extraction purification ranged from 93% to 96%. Conjugation of 18F-SFB to IL2 yielded 18F-FB-IL2 as the major product. The radiochemical yield of 18F-FB-IL2 after high-performance liquid chromatography purification was 25%–35% based on 18F-SFB. 18F-FB-IL2 was stable in plasma at 37°C and capable of stimulating T cells to an extent similar to native IL2. A biodistribution study showed highest tracer uptake in the kidneys and bladder due to rapid renal clearance of the tracer. Small-animal PET images showed binding of 18F-FB-IL2 to activated hPBMc proportional to the number of injected cells. Conclusion: We report the successful labeling of IL2 with 18F for PET of activated T lymphocytes. 18F-FB-IL2 is stable, is biologically active, and allows in vivo detection of activated T lymphocytes.