新的前列腺癌影像技术能显示实时肿瘤代谢

与通用电气医疗加州大学旧金山分校的研究合作中产生了一种新技术，有望迅速评估的存在和实时成像前列腺肿瘤的侵略性的肿瘤的新陈代谢，人类的第一批成果。

这是研究人员首次使用了这项技术在人类患者进行实时代谢显像，代表了革命的方法来评估肿瘤的准确概括，其对治疗的反应和它是如何迅速成长。

在第一例患者数据正今天在北美的为期一周的年度会议放射学会。

初步结果验证了广泛的临床前研究，已链接的速度肿瘤代谢营养，对他们的成长好斗的性格。新的成像技术也被用于实时显示及相应的药物治疗，不久，身体发生变化的动物肿瘤早期生化变化。

到目前为止，该技术已生产出在'人类患者的肿瘤，因为它没有在实验室研究中，即使在低剂量，同样的回应，根据萨拉尼尔森博士，放射学和生物医学影像学教授，加州理工学院的成员，定量生物科学（QB3）在加州大学旧金山分校。

“这是一个重要的里程碑，可以极大地改变对前列腺癌和许多其他肿瘤临床治疗中，”尼尔森说。 “我们证明了这在动物模型和组织样本的工作。如今，在男性中，我们看到正是我们所希望的结果类型。”

对于一个肿瘤，这意味着对病人是否应继续在“观察等待”或寻求治疗，也不管是工作的一种疗法，无论是在标准治疗或临床试验，并即时反馈。

“如果我们可以查看是否有治疗是实时有效的，我们也许能够在这治疗，可能对病人的成果和生活质量非常实际的影响早期的改变，”安德烈说Harzstark医师表示，肿瘤学家海伦与加州大学旧金山分校综合癌症中心的迪勒家庭谁是领先的，目前的研究在临床方面。

超过20万男性被诊断患有前列腺癌，每年死于28,000它，使它成为一个全国范围内的男性最常见的癌症，也是癌症死亡的主要原因之一，男性，根据美国疾病控制中心。

然而，疾病在其范围广泛的增长速度和侵略性，根据约翰Kurhanewicz，博士，加州大学旧金山分校的前列腺癌的影像学专家。因此，在有治疗疾病的理想策略的大辩论，他说，留下一个对如何积极应对困难和潜在的疾病改变生活的决定病人。

“这次测试可以给医师和患者的信息，他们需要做出决定，说：”Kurhanewicz，他们的工作与丹Vigneron，博士学位，并从放射学和生物医学成像加州大学旧金山分校署的同事首先与前列腺肿瘤的乳酸生产肿瘤的侵略性。其他研究人员也有联系的乳酸生产到肿瘤恶化和应对其他癌症疗法。

该方法利用正常组织功能所涉及的化合物 - 在这种情况下，丙酮酸，这是一个自然发生的副产物葡萄糖和乳酸也被称为乳酸 - 并使用新开发的设备，以增加对这些化合物的一个能见度50000因素磁共振成像（MRI）扫描仪。

这一过程需要丙酮酸在强磁场准备在摄氏零下272O，然后迅速加热到体温，转移到病人在核磁共振成像扫描仪的偏振衰变之前回到其原生状态。

其结果是对肿瘤的轮廓非常清晰的界定和形象，以及作为丙酮酸在肿瘤量图和速率肿瘤转化成乳酸丙酮酸。

无菌生产过程需要与双方的质量控制和临床实践知识的专门临床药师。作为临床药学领域，只有一间学校有少数药品生产的专业在全国的发祥地之一，加州大学旧金山分校的药学院和马库斯Ferrone，药学博士，并在药品服务实验室的同事捐款，这一进程的组成部分。

该过程必须在几分钟之内，这意味着整合成的扫描设备洁净室举行。 QB3还与GE医疗集团在设计拜尔斯大厅，其中高级成像Surbeck实验室安置，以适应极强的磁场的核磁共振成像扫描仪，使时间敏感实验。

“那就是为什么我们有识之士提出这项技术，北加州，”乔纳森说穆雷，总经理，在GE医疗代谢显像。 “这是一个巨大的成就，取得加州大学旧金山分校和QB3。他们汇集了来自加州大学旧金山分校的加州大学伯克利分校最好的工程，最好的生物科学和医药知识，而且现在也展示了世界著名的学术医疗中心的技术。我们很高兴与这种合作的进展速度。科学是非常兴奋。“

与第一次审判涉及在“观察等待”治疗前列腺癌的男性参与阶段，尼尔森说。未来的研究将直接比较与手术切除肿瘤，结果这些数据和将着眼于如何具体治疗肿瘤代谢的变化。加州大学旧金山分校也将是研究脑肿瘤患者在使用过程中。

该项目的通过生物医学成像与生物工程研究所，在美国国立卫生研究院的资金，关键是在适应这种技术为人类开发新的方法来获取数据的磁共振成像代谢。该项目得到了美国复苏与再投资法和UC探索项目的进一步支持。

本仪器及其证据展示的原则进行了初步的发展由Jan亨里克Ardenkjaer拉森Klaes Golman和其他同事来自全国各地通用。加州大学旧金山分校自定义的原则，并取得了研究性新药（IND）的美国食品和药物管理局批准使用的人类超极化丙酮酸。

这些概念仍研发中，并没有被出售，也没有被清除，或由FDA批准用于商业可用性。

A UCSF research collaboration with GE Healthcare has produced the first results in humans of a new technology that promises to rapidly assess the presence and aggressiveness of prostate tumors in real time, by imaging the tumor’s metabolism.

This is the first time researchers have used this technology to conduct real-time metabolic imaging in a human patient and represents a revolutionary approach to assessing the precise outlines of a tumor, its response to treatment and how quickly it is growing.

Data on the first four patients will be presented on Dec. 2 at the Radiology Society of North America’s weeklong annual conference.

The initial results validate extensive preclinical research that has linked the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.

So far, the technology has produced the same response in human patients’ tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of Radiology and Biomedical Imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF.

“This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors,” Nelson said. “We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for.”

For an oncologist, that means immediate feedback on whether a patient’s therapy is working, either during standard treatment or in a clinical trial.

“If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient’s outcome and quality of life,” said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.

More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancer in men nationwide and also one of the leading causes of cancer death in men, according to the Centers for Disease Control.

Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.

“This test could give both physicians and patients the information they need to make that decision,” said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumor’s production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.

The method uses compounds involved in normal tissue function – in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid – and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.

That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272° C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state.

The result is a highly defined and clear image of the tumor’s outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.

The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice. As the birthplace of the field of clinical pharmacy and one of only a handful of schools nationwide with drug production expertise, the UCSF School of Pharmacy and contributions of Marcus Ferrone, PharmD, and his colleagues in the Drug Products Services Laboratory were integral to this process.

The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.

“All of that insight is why we moved this technology to Northern California,” said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. “This is a huge accomplishment UCSF and QB3 have achieved. They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical center. We are delighted with the speed of progress of this collaboration. The science is very exciting.”

The first trial involves men with prostate cancer involved in the “watchful waiting” phase of treatment, Nelson said. Future studies will directly compare these data with the results from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.

The project’s funding through the National Institute of Biomedical Imaging and Bioengineering, in the National Institutes of Health, was critical in adapting this technology for humans and developing new ways to obtain the MR metabolic imaging data. The project received further support from the American Recovery & Reinvestment Act and the UC Discovery Program.

Initial development of this instrumentation and its demonstration of proof of principle was conducted by Jan Henrik Ardenkjaer-Larsen, Klaes Golman and other colleagues from across GE. UCSF customized that principle and obtained the Investigational New Drug (IND) approval from the Food and Drug Administration to use the hyperpolarized pyruvate in humans.

These concepts are still investigational and not being offered for sale, nor have they been cleared or approved by the FDA for commercial availability.

（from UCSF News Release）