The Relationship of Phthalocyanine 4 (Pc 4) Concentrations Measured Noninvasively to Outcome of Pc 4 Photodynamic Therapy in Mice

The Relationship of Phthalocyanine 4 (Pc 4) Concentrations Measured Noninvasively to Outcome of Pc 4 Photodynamic Therapy in Mice
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DOI:
10.1111/j.1751-1097.2009.00542.x
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发表时间:
2009-07-01
影响因子:
3.3
通讯作者:
Eiseman, Julie L.
Eiseman, Julie L.
中科院分区:
生物学3区
文献类型:
--
作者:
Bai, Lihua;Guo, Jianxia;Eiseman, Julie L.

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无创测量目标组织光敏剂浓度的能力将允许优化光动力疗法(PDT)并可以改善结果。在本研究中,我们评估了通过光学药代动力学系统 (OPS) 无创测量的照射前肿瘤酞菁 4 (Pc 4) 浓度是否与肿瘤对 PDT 的反应相关。荷有人乳腺癌异种移植物的小鼠仅用2 mg kg(-1) Pc 4 iv、仅激光照射(150 J cm(-2))、Pc 4 随后分次照射或Pc 4 随后连续照射进行治疗。当给药后48小时肿瘤与皮肤的Pc 4 浓度比达到最大值2.1时开始激光照射治疗。肿瘤中以及体外脂肪乳中的 Pc 4 浓度随着激光能量密度的增加呈单指数下降。 Pc 4-PDT 导致肿瘤显着消退,并且在 Pc 4 后接受分次或连续照射治疗的组中,肿瘤反应相似。Pc 4-PDT 后的肿瘤生长延迟与 PDT 前 24 小时 OPS 测量的肿瘤 Pc 4 浓度相关 (R-2 = 0.86)。在切除的肿瘤中,OPS 测量的 Pc 4 浓度与 HPLC 测量的浓度相似。因此,光敏剂浓度的 OPS 测量可用于协助安排 Pc 4-PDT。
The ability to noninvasively measure photosensitizer concentration at target tissues will allow optimization of photodynamic therapy (PDT) and could improve outcome. In this study, we evaluated whether preirradiation tumor phthalocyanine 4 (Pc 4) concentrations, measured noninvasively by the optical pharmacokinetic system (OPS), correlated with tumor response to PDT. Mice bearing human breast cancer xenografts were treated with 2 mg kg(-1) Pc 4 iv only, laser irradiation (150 J cm(-2)) only, Pc 4 followed by fractionated irradiation or Pc 4 followed by continuous irradiation. Laser irradiation treatment was initiated when the tumor to skin ratio of Pc 4 concentration reached a maximum of 2.1 at 48 h after administration. Pc 4 concentrations in tumor, as well as in Intralipid in vitro, decreased monoexponentially with laser fluence. Pc 4-PDT resulted in significant tumor regression, and tumor response was similar in the groups receiving either fractionated or continuous irradiation treatment after Pc 4. Tumor growth delay following Pc 4-PDT correlated with OPS-measured tumor Pc 4 concentrations at 24 h prior to PDT (R-2 = 0.86). In excised tumors, OPS-measured Pc 4 concentrations were similar to the HPLC-measured concentrations. Thus, OPS measurements of photosensitizer concentrations can be used to assist in the scheduling of Pc 4-PDT.