Cellular distribution by 2-photon fluorescence of complexes of metallic radioisotopes for imaging and therapy

使用放射性同位素（PET或SPECT成像）的诊断性医学成像是临床医生能够在治疗前后评估患者并监测进展的重要工具。许多使用的化合物含有放射性金属，如锝、铜和铟。在患者注射放射性化合物后，检测其放射出的辐射，可获得分辨率为1-2mm的图像，例如显示肿瘤的位置。然而，一旦进入人体，放射性化合物就会被细胞吸收，这就决定了显像剂针对疾病部位的效果。PET和SPECT成像不能用于揭示细胞内发生的事情，因为这些细胞的分辨率远小于1-2mm的极限。有些化合物在不同波长的辐射激发后会发出紫外线或可见光；这种现象被称为荧光。这比PET或SPECT具有更高的分辨率，我们建议使用这项技术来揭示潜在的金属基PET和SPECT显像剂在活细胞内的行为。这就要求设计的化合物不仅要针对特定的疾病部位，而且要具有荧光性。来自荧光的信息将提供有关化合物被困在目标疾病部位的机制的宝贵信息，然后可用于重新设计化合物以提高其成像性能。诊断成像现在是现代医学的一个关键部分，改进的PET和SPECT试剂将为患者获得更准确的诊断做出重大贡献，并使治疗能够根据个体患者的需求进行调整。这种个性化医疗的概念被全世界视为未来的主要目标。

Diagnostic medical imaging using radioactive isotopes (PET or SPECT imaging) is an important tool for clinicians to be able to assess patients both before and after treatment and thence to monitor progress. Many of the compounds used contain radioactive metals such as technetium, copper and indium. Detection of the radiation emitted from a patient following injection of the radioactive compound gives images with a resolution of 1-2mm which show for instance the location of a tumour. However once inside the body the radioactive compounds are taken up in cells and this can determine how effectively an imaging agent targets a disease site. PET and SPECT imaging cannot be used to uncover what happens within cells as these are much smaller than the resolution limit of 1-2mm. Some compounds will emit ultraviolet or visible radiation following excitation with radiation at a different wavelength; a phenomenon known as fluorescence. This has much higher resolution than PET or SPECT and we propose to use this technique to reveal how potential metal based PET and SPECT imaging agents are behaving within living cells. This requires the design of compounds that not only target specific disease sites but are also fluorescent. The information from fluorescence will give invaluable information about the mechanisms by which the compounds are trapped at the target disease sites and this can be then be used to redesign the compound to improve its imaging performance. Diagnostic imaging is now a key part of modern medicine and improved PET and SPECT agents would make a significant contribution to obtaining more accurate diagnosis for patients and enabling the treatment to be tailored to an individual patients needs. This concept of personalised medicine is seen worldwide as a major goal for the future.