School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Life Sciences Mass Spectrometry, Department of Analytical and Inorganic Chemistry, University of Geneva, Geneva, Switzerland.
J Control Release. 2018 Jan 10;269:128-135. doi: 10.1016/j.jconrel.2017.10.042. Epub 2017 Oct 31.
This study describes the use of fluorescence imaging and mass spectrometry imaging, for imaging the anti-angiogenic drug sunitinib, used to treat liver cancer. These techniques allowed for the assessment of local delivery of the unlabeled therapeutic drug. More specifically, the spatial distribution of the drug and its metabolites after local administration was investigated, and drug levels in tumor and liver tissue over time were quantified. For this purpose, sunitinib-eluting microspheres were locoregionally injected into the tumor feeding arteries of rabbits bearing liver tumors. In adjacent areas of tumor and non-targeted contralateral liver tissue, sunitinib distribution was mapped around beads in occluded vessels 7, 12, 13 and 14days after embolization by means of the two imaging methods. Presence of sunitinib metabolites was assessed by mass spectrometry imaging. Sunitinib was found around microspheres in the tumor at day 7, 12, and 13. The drug was retained by the necrotic tumor tissue, resulting in homogeneously distributed and high levels of up to 40μg/g tissue in a 1.5mm radius around the beads. The drug was almost completely eliminated from the contralateral liver tissue. Several of the drug's metabolites, including its primary active metabolite SU12662, were detected in the tumor tissue over 13days. Sunitinib diffused from the beads and was retained at high, therapeutic levels during 13days. This was confirmed independently by complementary fluorescence and mass spectrometry imaging, which served as tools to confirm effective drug delivery after hepatic transarterial administration in situ. Compound: Sunitinib: PubChem CID 5329102.
本研究描述了荧光成像和质谱成像在成像抗血管生成药物舒尼替尼（用于治疗肝癌）中的应用。这些技术可用于评估未标记治疗药物的局部递送。更具体地，研究了局部给药后药物及其代谢物的局部分布，并随时间定量了肿瘤和肝组织中的药物水平。为此，将载有舒尼替尼的微球局部注射到患有肝肿瘤的兔子的肿瘤供养动脉中。在栓塞后 7、12、13 和 14 天，通过两种成像方法在闭塞血管周围的珠子附近描绘了肿瘤和非靶向对侧肝组织中的舒尼替尼分布。通过质谱成像评估了舒尼替尼代谢物的存在。在栓塞后第 7、12 和 13 天，在肿瘤中发现了微球周围的舒尼替尼。药物被坏死的肿瘤组织保留，导致在珠子周围 1.5mm 半径内均匀分布并达到高达 40μg/g 组织的高浓度。药物几乎完全从对侧肝组织中消除。在肿瘤组织中检测到了药物的几种代谢物，包括其主要活性代谢物 SU12662。这一点在 13 天内通过补充荧光和质谱成像得到了独立证实，这两种成像方法作为工具用于确认肝动脉内给药原位后有效的药物递送。化合物：舒尼替尼：PubChem CID 5329102。
