Targeting 124I to the DNA of tumours for PET Imaging and Auger-Radiotherapy

该项目的目的是开发一种新的方法，利用放射性元素（碘-124）将放射性瞄准肿瘤，进行检测和治疗。碘-124放射出一种称为正电子的辐射形式，由一种新的成像技术-正电子发射断层扫描（PET）检测。因此，用碘-124标记的肿瘤可以通过PET成像。此外，碘-124是一类放射性原子（称为俄歇发射体），可以发射极低能量的电子簇。这种强烈的辐射损伤可以通过造成致命的DNA损伤来杀死癌细胞。为了使碘-124接近DNA分子，我们将它连接到与肿瘤蛋白质（如抗肿瘤抗体）连接的DNA结合药物上。注射放射性药物-蛋白质混合物后，PET成像将用于评估肿瘤靶向的程度，以计算通过进一步注射成功治疗肿瘤所需的混合物量。在某些情况下，肿瘤成像需要是非损伤性的，例如使用PET成像来评估手术切除肿瘤的成功率。因此，我们将设计一种碘-124标记的DNA结合药物的替代版本，其中放射性原子位于将放射性衰变对DNA损伤最小化的位置。在这种仅成像的情况下，俄歇发射特征被抑制，同时仍然利用正电子发射进行成像。放射性原子的稳定性差异很大，碘-124的半衰期（约4天）是成像和治疗的理想折衷。相比之下，PET成像最常用的同位素氟-18的效用受到其半衰期仅为几小时的限制。PeterMac的PET中心将很快生产碘-124，成为世界上为数不多的中心之一。Peter Mac最近为该项目开发的技术提交了专利申请。

The aim of this project is to develop a new method of targeting radioactivity to tumours, for detection and treatment, using a radioactive element (iodine-124). Iodine-124 emits a form of radiation called positrons, detected by a new imaging technique - Positron Emission Tomography (PET). Therefore, tumours labelled with iodine-124 can be imaged by PET. Also, iodine-124 is amongst a class of radioactive atoms (called Auger-emitters) that emit a shower of very low energy electrons. This intense focus of radiation damage, can be exploited to kill cancer cells by inflicting lethal DNA damage. To bring the iodine-124 close to the DNA molecule, we will attach it to a DNA-binding drug linked to a tumour-seeking protein, such as an anti-tumour antibody. After injection of the radioactive drug-protein cocktail, PET imaging will be used to assess the extent of tumour targeting, to enable calculation of the amount of cocktail required for successful tumour treatment by further injections. There are some situations where tumour imaging needs to be non-damaging, such as in using PET imaging to assess the success of surgical removal of a tumour. Therefore, we will design an alternative version of the iodine-124-labelled DNA- binding drug with the radioactive atom in a location that will minimise DNA damage from radioactive decay. In this imaging-only scenario, the Auger-emission feature is suppressed whilst still exploiting positron-emission for imaging. The stability of radioactive atoms varies widely, and the half-life of iodine-124 (about four days) is an ideal compromise for imaging and treatment. By contrast, the utility of the most commonly used isotope for PET imaging, fluorine-18, is limited by its half-life of only a few hours. The PET Centre at PeterMac will soon produce iodine-124, joining one of only a few centres throughout the world. Peter Mac has recently lodged a patent application for the technology to be developed in this project.