title: Radiopharmaceutical evaluation of (131)I-protohypericin as a necrosis avid compound.
abstract: 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 (131)I-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 (131)I-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 (131)I-protohypericin in necrotic tissues. These results suggest that (131)I-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.
authors: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , PR China .
authors: Xuejiao
authors: X
authors: Liu
authors: Yuanbo
authors: Y
authors: Feng
authors: Cuihua
authors: C
authors: Jiang
authors: Bin
authors: B
authors: Lou
authors: Yue
authors: Y
authors: Li
authors: Wei
authors: W
authors: Liu
authors: Nan
authors: N
authors: Yao
authors: Meng
authors: M
authors: Gao
authors: Yun
authors: Y
authors: Ji
authors: Qingqing
authors: Q
authors: Wang
authors: Dejian
authors: D
authors: Huang
authors: Zhiqi
authors: Z
authors: Yin
authors: Ziping
authors: Z
authors: Sun
authors: Yicheng
authors: Y
authors: Ni
authors: Jian
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D006207:Half-Life; D007238:Infarction; D007457:Iodine Radioisotopes; D008099:Liver / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C108325:protohypericin; D010569:Perylene
keywords: Aggregation; biodistribution; necrosis affinity; pharmacokinetics; protohypericin