Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (⁶⁸Ga) through a straightforward conjugation reaction. Polyethylenimine (PEI)-decorated calcium alginate microspheres (PEI-CAMSs) were fabricated and further modified using azadibenzocyclooctyne-N-hydroxysuccinimide ester (ADIBO-NHS). Subsequently, azide-functionalized NOTA chelator (N₃-NOTA) was labeled with [⁶⁸Ga]Ga to obtain [⁶⁸Ga]Ga-NOTA-N₃, which was then reacted with the surface-modified PEI-CAMSs using strain-promoted alkyne-azide cycloaddition (SPAAC) reaction to develop [⁶⁸Ga]Ga-NOTA-PEI-CAMSs, a novel PET microsphere. The radiolabeling efficiency and radiochemical stability of [⁶⁸Ga]Ga-NOTA-PEI-CAMSs were determined using the radio-instant thin-layer chromatography-silica gel (radio-ITLC-SG) method. The in vivo PET images were also acquired to study the in vivo stability of the radiolabeled microspheres in normal mice. The radiolabeling efficiency of [⁶⁸Ga]Ga-NOTA-PEI-CAMSs was over 99%, and the microspheres exhibited high stability (92%) in human blood serum. PET images demonstrated the stability and biodistribution of the microspheres in mice for up to 2 h post injection. This study highlights the potential of biodegradable PET microspheres for preoperative imaging and targeted radionuclide therapy. Overall, the straightforward synthesis method and efficient radiolabeling technique provide a promising platform for the development of theranostic microspheres using other radionuclides such as ⁹⁰Y, ¹⁷⁷Lu, ¹⁸⁸Re, and ⁶⁴Cu.

Keywords: Gallium-68; alginate; biodegradable; positron emitters; radiochemical stability; radiolabeled microspheres.

生物可降解的放射性微球，标记有正电子发射体，在癌症和其他疾病（包括关节炎）的诊断和治疗应用中展现出巨大的潜力。基于海藻酸的聚合物微球具有生物相容性、生物降解性和改进稳定性等优点，使其适合临床应用。在这项研究中，我们使用海藻酸生物聚合物通过简单的偶联反应标记⁶⁸Ga（镓-68）开发了新型正电子发射断层成像（PET）微球。制备了聚乙烯亚胺（PEI）修饰的钙海藻酸盐微球（PEI-CAMSs），并进一步使用偶氮二苯并环辛炔-N-羟基琥珀酰亚胺酯（ADIBO-NHS）进行了表面修饰。随后，用⁶⁸Ga标记了带叠氮功能的NOTA螯合剂（N₃-NOTA），以获得⁶⁸Ga-NOTA-N₃，并通过应变促进的炔-叠氮环加成（SPAAC）反应将其与表面修饰后的PEI-CAMSs反应，开发了新型PET微球⁶⁸Ga-NOTA-PEI-CAMSs。使用放射性薄层色谱法-硅胶（radio-ITLC-SG）方法确定了⁶⁸Ga-NOTA-PEI-CAMSs的标记效率和放射化学稳定性。in vivoPET图像也用于研究正常小鼠体内标记微球的稳定性。⁶⁸Ga-NOTA-PEI-CAMSs的标记效率超过99%，并且微球在人血清中表现出高稳定性（92%）。PET图像显示，注射后长达2小时，小鼠体内的微球具有稳定性和生物分布。本研究强调了可降解PET微球用于术前成像和靶向放射性核素治疗的潜力。总的来说，简单的合成方法和高效的标记技术为使用其他放射性同位素（如⁹⁰Y、¹⁷⁷Lu、¹⁸⁸Re 和 ⁶⁴Cu）开发诊断-治疗微球提供了一个有前景的平台。

关键词： 镓-68；海藻酸盐；生物可降解性；正电子发射体；放射化学稳定性；标记微球。