Radiometals produced by liquid targets for molecular imaging of cancer

新的乳腺癌药物越来越多地针对与癌症进展有关的特定蛋白质，如表皮生长因子受体（HER2）。这些新药通常只能使一小部分患者受益，而且医疗保健系统的成本非常高（针对HER2的赫赛汀每年每位患者的成本超过4万美元）。在选择这些昂贵的治疗方法之前，医生需要了解患者肿瘤中是否存在药物靶点。预测蛋白的存在，也称为生物标志物，可以通过使用特殊的实验室技术进行肿瘤活检来确定。然而，通常不可能对已经扩散的肿瘤进行活检，并且生物标志物的含量可能因肿瘤部位而异。分子成像技术，如正电子发射断层扫描与计算机断层扫描（PET/CT）相结合，可以成为一种强大的、非侵入性的检测生物标志物的工具，使用极低浓度的放射性探针。该项目的目的是开发用于PET/CT成像的新型放射性同位素生产技术。利用这些放射性同位素，该项目将开发新的显像剂，使医生能够发现患者是否表达HER2变异，这种变异与目前用于治疗HER2阳性乳腺癌的药物的耐药性有关。我们感兴趣的放射性同位素分别是锆-89、镓-68、钇-86和钪-44。这些放射性同位素中有许多目前在加拿大无法获得。传统的生产方法涉及使用固体靶，由回旋加速器照射，但这种方法需要大多数设施无法获得的特定设备和专门知识。我们的多学科专家团队，以及我们的合作者和工业合作伙伴，将进行放射性同位素产量的理论模拟，设计新的盐溶液目标来制造放射性同位素，优化这些放射性同位素的生产条件，开发分离和纯化它们的方法，并将同位素附着在上面

New breast cancer drugs are increasingly targeted to specific proteins involved in cancer progression, such as the epidermal growth factor receptor (HER2). These new drugs typically benefit only a small proportion of patients, at very high cost to the health care system (over $40,000 per patient per year for Herceptin, which targets HER2). Physicians need information about whether a drug target is present in patients' tumours before selecting these expensive treatments. The presence of a predictive protein, also called a biomarker, can be determined by taking a tumour biopsy using special laboratory techniques. However, it is often impossible to biopsy tumours that have spread, and biomarker content may vary from one tumour site to another. Molecular imaging technologies such as positron emission tomography combined with computed tomography (PET/CT) can be a powerful, non invasive tool to detect biomarkers, using extremely low concentrations of radioactive probes. The purpose of this project is to develop novel radioisotope production technologies used for PET/CT imaging. With these radioisotopes, the project will develop new imaging agents that will allow physicians to find out if patients express a variant of HER2 that is associated with resistance to the current drug used to treat HER2 positive breast cancers. The radioisotopes of interest are called zirconium-89, gallium-68, yttrium-86 and scandium-44. Many of these radioisotopes are currently unavailable in Canada. The traditional production methods to make them involve the use of solid targets, which are irradiated by a cyclotron, but this approach requires specific equipment and expertise unavailable in most facilities. Our multidisciplinary team of experts, along with our collaborators and industrial partner, will conduct theoretical simulation of radioisotope production yields, design new salt-solution targets to make the radioisotopes, optimize the production conditions of these radioisotopes, develop methods to separate and purify them, and attach the isotopes to