Radiopharmaceutical evaluation of ¹³¹I-protohypericin as a necrosis avid compound

Hypericin is a necrosis avid agent useful for nuclear imaging and tumor therapy. Protohypericin, with a similar structure to hypericin except poorer planarity, is the precursor of hypericin. In this study, we aimed to investigate the impact of this structural difference on self-assembly, and evaluate the necrosis affinity and metabolism in the rat model of reperfused hepatic infarction. Protohypericin appeared less aggregative in solution compared with hypericin by fluorescence analysis. Biodistribution data of 131I-protohypericin showed the percentage of injected dose per gram of tissues (%ID/g) increased with time and reached to the maximum of 7.03 at 24 h in necrotic liver by gamma counting. The maximum ratio of target/non-target tissues was 11.7-fold in necrotic liver at 72 h. Pharmacokinetic parameters revealed that the half-life of 131I-protohypericin was 14.9 h, enabling a long blood circulation and constant retention in necrotic regions. SPECT-CT, autoradiography, and histological staining showed high uptake of 131I-protohypericin in necrotic tissues. These results suggest that 131I-protohypericin is a promising necrosis avid compound with a weaker aggregation tendency compared with hypericin and it may have a broad application in imaging and oncotherapy.金丝桃素（Hypericin）是一种可用于核成像与肿瘤治疗的坏死亲和型制剂。原金丝桃素（Protohypericin）的结构与金丝桃素相近，但平面性更差，是金丝桃素的前体。本研究旨在探究该结构差异对自组装过程的影响，并在大鼠再灌注性肝梗死模型中评估其坏死亲和性与代谢特性。荧光分析结果显示，与金丝桃素相比，原金丝桃素在溶液中的聚集倾向更低。131I-原金丝桃素的生物分布数据表明，经γ计数检测，每克组织的注射剂量百分比（%ID/g）随时间推移逐渐升高，并在坏死肝组织中于24小时达到峰值7.03。靶/非靶组织的最大比值在72小时于坏死肝组织中达到11.7倍。药代动力学参数显示，131I-原金丝桃素的半衰期为14.9小时，可实现较长的血液循环时间，并在坏死区域持续滞留。SPECT-CT、放射自显影及组织学染色结果均证实，131I-原金丝桃素在坏死组织中具有较高摄取量。上述结果表明，与金丝桃素相比，131I-原金丝桃素是一种聚集倾向更低、极具应用前景的坏死亲和型化合物，有望在成像技术与肿瘤治疗领域实现广泛应用。