The University of Sydney, Faculty of Science, School of Physics, Sydney, NSW, Australia.
Bill Walsh Translational Cancer Research Laboratory, The Kolling Institute, Northern Sydney Local Health District, Sydney, Australia.
Int J Nanomedicine. 2020 Jan 7;15:31-47. doi: 10.2147/IJN.S227931. eCollection 2020.
PURPOSE: Using our chelate-free, heat-induced radiolabeling (HIR) method, we show that a wide range of metals, including those with radioactive isotopologues used for diagnostic imaging and radionuclide therapy, bind to the Feraheme (FH) nanoparticle (NP), a drug approved for the treatment of iron anemia. MATERIAL AND METHODS: FH NPs were heated (120°C) with nonradioactive metals, the resulting metal-FH NPs were characterized by inductively coupled plasma mass spectrometry (ICP-MS), dynamic light scattering (DLS), and r and r relaxivities obtained by nuclear magnetic relaxation spectrometry (NMRS). In addition, the HIR method was performed with [Y]Y, [Lu]Lu, and [Cu]Cu, the latter with an HIR technique optimized for this isotope. Optimization included modifying reaction time, temperature, and vortex technique. Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and thin-layer chromatography (TLC). RESULTS: With ICP-MS, metals incorporated into FH at high efficiency were bismuth, indium, yttrium, lutetium, samarium, terbium and europium (>75% @ 120 C). Incorporation occurred with a small (less than 20%) but statistically significant increases in size and the r relaxivity. An improved HIR technique (faster heating rate and improved vortexing) was developed specifically for copper and used with the HIR technique and [Cu]Cu. Using SEC and TLC analyses with [Y]Y, [Lu]Lu and [Cu]Cu, RCYs were greater than 85% and RCPs were greater than 95% in all cases. CONCLUSION: The chelate-free HIR technique for binding metals to FH NPs has been extended to a range of metals with radioisotopes used in therapeutic and diagnostic applications. Cations with f-orbital electrons, more empty d-orbitals, larger radii, and higher positive charges achieved higher values of RCY and RCP in the HIR reaction. The ability to use a simple heating step to bind a wide range of metals to the FH NP, a widely available approved drug, may allow this NP to become a platform for obtaining radiolabeled nanoparticles in many settings.
目的：利用我们的无螯合物、热诱导放射性标记（HIR）方法，我们表明，包括用于诊断成像和放射性核素治疗的放射性同位素的各种金属，都与 Feraheme（FH）纳米颗粒（NP）结合，FH NP 是一种批准用于治疗铁贫血的药物。
材料和方法：将 FH NPs 加热（120°C）与非放射性金属一起，通过电感耦合等离子体质谱（ICP-MS）、动态光散射（DLS）和通过磁共振弛豫谱（NMRS）获得的 r 和 r 弛豫率来表征所得的金属-FH NPs。此外，还使用 [Y]Y、[Lu]Lu 和 [Cu]Cu 进行了 HIR 方法，后一种方法使用针对该同位素优化的 HIR 技术。优化包括修改反应时间、温度和涡旋技术。使用尺寸排阻色谱（SEC）和薄层层析（TLC）测量放射性化学收率（RCY）和纯度（RCP）。
结果：使用 ICP-MS，以高效率将铋、铟、钇、镥、钐、铽和铕掺入 FH 中（>75%@120°C）。掺入发生在尺寸略有增加（小于 20%）但具有统计学意义的情况下，并且 r 弛豫率也略有增加。专门为铜开发了一种改进的 HIR 技术（更快的加热速率和改进的涡旋），并与 HIR 技术和 [Cu]Cu 一起使用。使用 SEC 和 TLC 分析与 [Y]Y、[Lu]Lu 和 [Cu]Cu，在所有情况下，RCY 均大于 85%，RCP 均大于 95%。
结论：用于将金属结合到 FH NPs 的无螯合物 HIR 技术已扩展到用于治疗和诊断应用的一系列具有放射性同位素的金属。具有 f 轨道电子、更多空 d 轨道、更大半径和更高正电荷的阳离子在 HIR 反应中实现了更高的 RCY 和 RCP 值。使用简单的加热步骤将广泛可用的批准药物 FH NP 与各种金属结合的能力，可能使该 NP 成为在许多情况下获得放射性标记纳米颗粒的平台。
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