Dependence of photoacoustic signal generation characteristics on fluorescence quantum yields of small organic molecule based contrast agents
Dependence of photoacoustic signal generation characteristics on fluorescence quantum yields of small organic molecule based contrast agents
复制标题
光声信号生成特性对小有机分子造影剂荧光量子产率的依赖性
DOI：
10.1117/12.2255594
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
M Ishihara
中科院分区：
文献类型：
--
作者：
T Hirasawa;RJ Iwatate;M Kamiya;S Okawa;Y Urano;M Ishihara
光声成像（PA）在造影剂成像中具有优势，因为它在生物组织内部超过几毫米的深度具有很高的空间分辨率。为了特异性检测小肿瘤，我们正在开发基于有机小分子的可活化PA探针，其机制类似于已成功用于小肿瘤快速荧光成像的酶活化荧光探针。探针也可以通过荧光成像成像，荧光图像可以合并到PA图像上。为了通过增加PA信号强度来扩大成像深度，需要高效产生PA信号的PA探头。为了选择适合于PA探针的小有机分子，我们合成了具有不同吸收光谱和荧光量子产率的小有机分子造影剂，然后我们详尽地评估了它们的PA信号产生特性，包括PA信号产生效率。为了准确分析造影剂的信号产生效率，利用P（VDF-TrFE）压电薄膜声传感器测量了造影剂水溶液中产生的声压绝对值。因此，具有低荧光量子产率的小有机分子可以有效地产生PA信号。因此，与荧光探针相反，PA探针应该具有较低的荧光量子产率。综合考虑结果和激发波长等其他特性，我们可以筛选出适合于PA探针的有机小分子。合成了低荧光量子产率、激发波长大于600 nm的可活化PA探针，并通过体外实验对其特异性进行了检测。
Photoacoustic (PA) imaging is advantageous in contrast agent imaging because of high spatial resolution at depth more than several millimeter inside biological tissues. To detect small tumors specifically, we are developing small organic molecule-based activatable PA probe with mechanism similar to that of the enzyme-activatable fluorescence probe that have successfully used for rapid fluorescence imaging of small tumors. The probe can be imaged also by fluorescence imaging and the fluorescence image can be merged onto the PA images. To extend the imaging depth by increasing PA signal intensity, PA probe that produce PA signals efficiently is required. To select small organic molecules suitable for PA probe, we synthesized small-organic molecule-based contrast agents with various absorption spectra and fluorescence quantum yields and then we exhaustively evaluated their PA signal generation characteristics including PA signal generation efficiencies. To analyze PA signal generation efficiencies precisely, the absolute values of PA signal pressures produced from aqueous solutions of the contrast agents were measured by P(VDF-TrFE) piezoelectric film acoustic sensor. As a result, small organic molecule with low fluorescence quantum yield produced PA signals efficiently. Thus, as opposed to fluorescence probes, PA probes should have low fluorescence quantum yields. By considering the result and other characteristics including excitation wavelengths, we could single out the small organic molecule suitable for PA probe. We synthesized the new activatable PA probe with low fluorescence quantum yield and excitation wavelength longer than 600 nm and its specificity was examined inin vitroexperiment.