新的前列腺癌影像技術能顯示實時腫瘤代謝

與通用電氣醫療加州大學舊金山分校的研究合作中產生了一種新技術，有望迅速評估的存在和實時成像前列腺腫瘤的侵略性的腫瘤的新陳代謝，人類的第一批成果。

這是研究人員首次使用了這項技術在人類患者進行實時代謝顯像，代表了革命的方法來評估腫瘤的準確概括，其對治療的反應和它是如何迅速成長。

在第一例患者數據正今天在北美的為期一周的年度會議放射學會。

初步結果驗證了廣泛的臨床前研究，已鏈接的速度腫瘤代謝營養，對他們的成長好鬥的性格。新的成像技術也被用於實時顯示及相應的藥物治療，不久，身體發生變化的動物腫瘤早期生化變化。

到目前為止，該技術已生產出在'人類患者的腫瘤，因為它沒有在實驗室研究中，即使在低劑量，同樣的回應，根據薩拉尼爾森博士，放射學和生物醫學影像學教授，加州理工學院的成員，定量生物科學（QB3）在加州大學舊金山分校。

“這是一個重要的裏程碑，可以極大地改變對前列腺癌和許多其他腫瘤臨床治療中，”尼爾森說。 “我們證明了這在動物模型和組織樣本的工作。如今，在男性中，我們看到正是我們所希望的結果類型。”

對於一個腫瘤，這意味著對病人是否應繼續在“觀察等待”或尋求治療，也不管是工作的一種療法，無論是在標準治療或臨床試驗，並即時反饋。

“如果我們可以查看是否有治療是實時有效的，我們也許能夠在這治療，可能對病人的成果和生活質量非常實際的影響早期的改變，”安德烈說Harzstark醫師表示，腫瘤學家海倫與加州大學舊金山分校綜合癌症中心的迪勒家庭誰是領先的，目前的研究在臨床方麵。

超過20萬男性被診斷患有前列腺癌，每年死於28,000它，使它成為一個全國範圍內的男性最常見的癌症，也是癌症死亡的主要原因之一，男性，根據美國疾病控製中心。

然而，疾病在其範圍廣泛的增長速度和侵略性，根據約翰Kurhanewicz，博士，加州大學舊金山分校的前列腺癌的影像學專家。因此，在有治療疾病的理想策略的大辯論，他說，留下一個對如何積極應對困難和潛在的疾病改變生活的決定病人。

“這次測試可以給醫師和患者的信息，他們需要做出決定，說：”Kurhanewicz，他們的工作與丹Vigneron，博士學位，並從放射學和生物醫學成像加州大學舊金山分校署的同事首先與前列腺腫瘤的乳酸生產腫瘤的侵略性。其他研究人員也有聯係的乳酸生產到腫瘤惡化和應對其他癌症療法。

該方法利用正常組織功能所涉及的化合物 - 在這種情況下，丙酮酸，這是一個自然發生的副產物葡萄糖和乳酸也被稱為乳酸 - 並使用新開發的設備，以增加對這些化合物的一個能見度50000因素磁共振成像（MRI）掃描儀。

這一過程需要丙酮酸在強磁場準備在攝氏零下272O，然後迅速加熱到體溫，轉移到病人在核磁共振成像掃描儀的偏振衰變之前回到其原生狀態。

其結果是對腫瘤的輪廓非常清晰的界定和形象，以及作為丙酮酸在腫瘤量圖和速率腫瘤轉化成乳酸丙酮酸。

無菌生產過程需要與雙方的質量控製和臨床實踐知識的專門臨床藥師。作為臨床藥學領域，隻有一間學校有少數藥品生產的專業在全國的發祥地之一，加州大學舊金山分校的藥學院和馬庫斯Ferrone，藥學博士，並在藥品服務實驗室的同事捐款，這一進程的組成部分。

該過程必須在幾分鍾之內，這意味著整合成的掃描設備潔淨室舉行。 QB3還與GE醫療集團在設計拜爾斯大廳，其中高級成像Surbeck實驗室安置，以適應極強的磁場的核磁共振成像掃描儀，使時間敏感實驗。

“那就是為什麽我們有識之士提出這項技術，北加州，”喬納森說穆雷，總經理，在GE醫療代謝顯像。 “這是一個巨大的成就，取得加州大學舊金山分校和QB3。他們匯集了來自加州大學舊金山分校的加州大學伯克利分校最好的工程，最好的生物科學和醫藥知識，而且現在也展示了世界著名的學術醫療中心的技術。我們很高興與這種合作的進展速度。科學是非常興奮。“

與第一次審判涉及在“觀察等待”治療前列腺癌的男性參與階段，尼爾森說。未來的研究將直接比較與手術切除腫瘤，結果這些數據和將著眼於如何具體治療腫瘤代謝的變化。加州大學舊金山分校也將是研究腦腫瘤患者在使用過程中。

該項目的通過生物醫學成像與生物工程研究所，在美國國立衛生研究院的資金，關鍵是在適應這種技術為人類開發新的方法來獲取數據的磁共振成像代謝。該項目得到了美國複蘇與再投資法和UC探索項目的進一步支持。

本儀器及其證據展示的原則進行了初步的發展由Jan亨裏克Ardenkjaer拉森Klaes Golman和其他同事來自全國各地通用。加州大學舊金山分校自定義的原則，並取得了研究性新藥（IND）的美國食品和藥物管理局批準使用的人類超極化丙酮酸。

這些概念仍研發中，並沒有被出售，也沒有被清除，或由FDA批準用於商業可用性。

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）