MICA: Molecular imaging of HER2 receptor expression using PET: mechanistic study of the novel [18F]-HER2-Affibody tracer in metastatic breast cancer

在英国，每8名女性中就有1人会患上乳腺癌，其中20%的人会患上HER2阳性的癌症，这意味着肿瘤的癌细胞表面有一个蛋白质受体。HER2受体的存在被发现会使癌症更具侵袭性，通常情况下，他们的结果比HER2阴性的肿瘤更糟糕。HER2阳性乳腺癌可以用曲妥珠单抗(又称赫赛汀)等药物治疗，曲妥珠单抗在早期用于降低复发风险，或在转移阶段使用，当癌症扩散到远处器官时试图控制疾病。这项研究旨在为HER2阳性乳腺癌患者开发一种新型的扫描方法。这项测试涉及一种非常少量的放射性化学物质(称为示踪剂)，它可以与HER2受体结合。这种示踪剂可以在PET扫描仪中检测到，并用于定位HER2阳性的区域。目前，医生依靠肿瘤的活组织检查来检测HER2，活组织检查可能会很痛苦，而且并不总是可能从身体的某些部位进行检查，例如，如果肿瘤靠近血管，活组织检查可能会导致出血。在晚期癌症患者(意味着肿瘤已经扩散到身体的远处)，已经开发出针对HER2受体的新药。与标准治疗相比，新药的应答率要高得多，被誉为治疗HER2阳性癌症的突破。然而，这种疾病的预后仍然很差，临床研究表明，20%到50%的转移性HER2阳性癌症患者对一些新的药物没有反应。耐药性只有在接受了几种治疗后才会变得明显，通常在CT扫描中发现，要么显示新的病变，要么显示现有的肿瘤病变扩大。较新的药物确实有很大的副作用风险，包括低血小板(帮助血液凝结12%)和心脏毒性(1%)。但对于个别患者，我们无法在治疗开始前预测他们的转移肿瘤是否对治疗有反应，也不可能对每个病灶进行活组织检查。这项研究将分为两个阶段，在第一阶段，我们将评估HER2阳性肿瘤是否比HER2阴性肿瘤更多地使用示踪剂，这将涉及总共16名患者持续约90分钟的详细PET扫描，由于示踪剂(也称为Ge-226)以前从未在这种特定形式中使用过，我们还将通过在扫描前后仔细监测患者来研究安全性，这一阶段将在伦敦的一个中心(帝国理工学院)进行，该中心在这类研究方面具有特殊的专业知识，如果这一阶段成功并且没有重大毒性，我们将进入第二阶段，这将涉及25名HER2阳性患者，他们将在四个中心中的一个中心(以最近者为准)进行GE-226 PET扫描，PET扫描将在一个疗程开始时进行，并与标准CT扫描进行比较，标准CT扫描是在治疗前和治疗3个周期(63天)之后进行的，以衡量PET扫描的结果是否可以预测哪些患者对治疗有反应。在研究开始之前，我们将获得所有相关委员会(伦理、辐射、MHRA)的监管批准。我们希望这个项目的结果是证明Ge-226在HER2阳性疾病中有更高的摄取率，它是安全的和良好的耐受性，并且它可以预测治疗反应。如果这是成功的，那么未来可能会进行更大规模的研究来证实这一点，最终这可能成为这组患者的常规测试，这将帮助肿瘤学家选择最佳治疗方法，并降低NHS的药品成本。这项研究将由来自英国的顶尖肿瘤学家和成像科学家领导。

1 in 8 women in the UK will develop breast cancer, 20% of whom will have cancer which is her2 positive - meaning that the tumours have a protein receptor on the surface of the cancer cells. The presence of the her2 receptor has been found to make cancers more aggressive, and generally their outcomes are worse than those tumours that are her2 negative. Her2 positive breast cancer can be treated with drugs such as trastuzumab (otherwise known as Herceptin) which is used in the early stages to reduce the risk of relapse, or in the metastatic stage when the cancer has spread to distant organs to try and control the disease.This study aims to develop a new type of scan for imaging patients with her2 positive breast cancer. The test involves a very small amount of a radioactive chemical (called a tracer), which can bind to the her2 receptor. This tracer can be detected in a PET scanner and used to localise the areas that are her2 positive. At present doctors rely on biopsies of tumours to detect her2, the biopsies can be painful and are not always possible from certain areas of the body for example the biopsy might cause bleeding if the tumour is near a blood vessel. In patients with advanced cancer (meaning that the tumour has spread to distant parts of the body) new drugs have been developed which target the her2 receptor.Compared to standard treatments the newer drugs have significantly higher response rates and have been hailed as breakthroughs in the treatment of her2 positive cancer. However the prognosis for this disease remains poor, and the clinical studies show that between 20 and 50% of patients with metastatic her2 positive cancer will not respond to some of these newer agents. Resistance only becomes apparent after several treatments have been given, and is generally found in CT scans which show either new lesions or that the existing tumour lesions have enlarged in size. The newer drugs do have a significant risk of side effects including low platelets (which help the blood to clot in 12%), and heart toxicity (1%).However for individual patients we cannot predict before the start of treatment if their metastatic tumours will respond to treatment, and it is not possible to biopsy every single lesion. This study will be divided into two phases, in the first phase we will assess whether the tracer is taken up more in her2 positive tumours than her2 negative tumours, this will involve detailed PET scans lasting approximately 90 minutes in 16 patients in total, as the tracer (also known as GE-226) has not been used in this specific form before, we will also study safety by monitoring patients carefully before and after the scans, this phase will all be done in one centre in London (Imperial College) which has particular expertise in this type of study, if this phase is successful and there is no significant toxicity we will proceed to the second phase which will involve 25 patients with her2 positive patients who will have a PET scan with GE-226 in one of four centres (whichever is closest), the PET scan will be done at the start of a course of therapy and compared to standard CT scans which are done before treatment and after 3 cycles of treatment (63 days) to measure if the findings from the PET scan can predict which patients will respond to treatment. We will have regulatory approval from all the relevant committees in place (ethics, radiation, MHRA) before the study can start. The outcomes for this project we hope for are to demonstrate that GE-226 has higher uptake in her2 positive disease, that it is safe and well tolerated, and that it can predict response to treatment. If this is successful then larger studies could be done in the future to confirm this, and eventually this could become a routine test in this group of patients which would help oncologists select the best treatments, and also reduce drug costs for the NHS. The study will be led by leading oncologists and imaging scientists from the UK.