Cona Marlein Miranda, Feng Yuanbo, Zhang Jian, Li Yue, Verbruggen Alfons, Oyen Raymond, Ni Yicheng
Department of Imaging and Pathology, Faculty of Medicine, Biomedical Sciences Group , KU Leuven, Leuven , Belgium .
Drug Deliv. 2015 May;22(3):427-35. doi: 10.3109/10717544.2013.873838. Epub 2014 Jan 13.
We determined whether sodium cholate (NaCh) could act as a solubilizing agent for the necrosis avid iodine-123-labeled hypericin ((123)I-Hyp) and investigated biodistribution and targetability of this formulation in rabbits with acute myocardial infarction (AMI).
Solubility of radioiodinated hypericin/hypericin (Hyp) in NaCh solutions was evaluated by microscopy. Hyp with (123)I-sodium iodide was performed using hydrogen peroxide as oxidant in 0.06 M NaCh. Radiochemical yield determination and purification were conducted using high performance liquid chromatography. (123)I-Hyp was solubilized in 0.06 M NaCh containing 1.9 × 10(-4 )M Hyp. The formulation was macroscopically inspected and intravenously injected to five rabbits with AMI. At 24 h, biodistribution was evaluated by tissue gamma counting (TGC) and necrosis targetability was assessed by TGC, autoradiography, fluorescence examination and histology.
Microscopically NaCh at 0.06 M shows the best properties for solubilizing the radioiodinated Hyp/Hyp. (123)I-Hyp in 0.06 M NaCh was achieved in 85% with radiochemical purity of 99% after purification. NaCh-dissolved (123)I-Hyp/Hyp shows no particles. By TGC, animals exhibited higher (p = 0.003) radioactivity accumulation in AMI (0.8 ± 0.2% ID/g) than in normal myocardium (0.05 ± 0.02% ID/g), as confirmed by autoradiography, fluorescence measurement and histology. Among organs, the highest uptake of radioactivity was found in liver (15.7 ± 0.6% ID), large (9.7 ± 1.0% ID) and small (5.9 ± 0.6% ID) intestines.
Necrosis avidity of NaCh-dissolved (123)I-Hyp/Hyp and its hepatobiliary excretion were demonstrated. The suitability of NaCh as solubilizing agent of (123)I-Hyp for hotspot imaging of AMI was proved.
我们确定了胆酸钠（NaCh）是否可作为坏死亲和性碘 - 123标记的金丝桃素（（123）I - Hyp）的增溶剂，并研究了该制剂在急性心肌梗死（AMI）兔中的生物分布和靶向性。
通过显微镜评估放射性碘化金丝桃素/金丝桃素（Hyp）在NaCh溶液中的溶解度。在0.06 M NaCh中，以过氧化氢作为氧化剂进行用（123）I - 碘化钠标记Hyp。使用高效液相色谱法进行放射化学产率测定和纯化。将（123）I - Hyp溶解在含有1.9×10（-4）M Hyp的0.06 M NaCh中。对该制剂进行宏观检查，并静脉注射给5只AMI兔。在24小时时，通过组织γ计数（TGC）评估生物分布，并通过TGC、放射自显影、荧光检查和组织学评估坏死靶向性。
显微镜下观察，0.06 M的NaCh对放射性碘化Hyp/Hyp具有最佳的增溶性能。纯化后，在0.06 M NaCh中制备的（12）I - Hyp产率为85%，放射化学纯度为99%。NaCh溶解的（123）I - Hyp/Hyp无颗粒。通过TGC，动物AMI区域（0.8±0.2% ID/g）的放射性积累高于正常心肌（0.05±0.02% ID/g）（p = 0.003），放射自显影、荧光测量和组织学证实了这一点。在各器官中，肝脏（15.7±0.6% ID）、大肠（9.7±1.0% ID）和小肠（5.9±0.6% ID）的放射性摄取最高。
证实了NaCh溶解的（123）I - Hyp/Hyp的坏死亲和性及其肝胆排泄。证明了NaCh作为（123）I - Hyp增溶剂用于AMI热点成像的适用性。
