2008 Results

University of California San Francisco Institute for Quantitative Biomedical Research

Prostate cancer imaging research at the University of California, San Francisco has benefited greatly from the generous support of the Sir Peter and Lady Michael Foundation. Under the direction of Professor Daniel Vigneron, Ph.D., the research focuses on developing improved methods for anatomic and metabolic Magnetic Resonance imaging (MRI) of prostate cancer. Such improved imaging is critical for guiding and evaluating emerging therapies. Also, these methods allow noninvasive monitoring on patients who have deferred treatment and are under “active surveillance”. The need for improved prostate cancer imaging was clearly stated in the consensus of participants of the Colloquium on Prostate Cancer, sponsored by the Pelican Cancer Foundation this past May in the United Kingdom. This continues to be an under-funded area of research, but a very necessary one that offers great potential benefit to prostate cancer patients.

The funding from the Sir Peter and Lady Michael Foundation has supported the effort of talented young imaging PhD scientists as Pelican Fellows researching new prostate cancer imaging methods for diagnosing as well as guiding and monitoring treatment. For two years up until this past April, Dr. Albert Chen has been the Pelican Fellow at UCSF. His work has resulted in new magnetic resonance (MR) techniques that double the spatial resolution of MR anatomic and metabolic imaging and reduce the time as compared to currently commercially available techniques. Dr. Chen’s work has resulted in a number of publications and he also presented his work on new metabolic imaging techniques to follow therapy response at the May meeting of the International Society of Magnetic Resonance in Medicine in Toronto. Dr. Chen accepted a position at GE Healthcare leading the Biochemical Imaging group on the east coast. His new industry position is focused on improving imaging techniques for a wide range of applications including prostate cancer.

Dr. Peder Larson became the current Pelican Fellow at UCSF last April and has rapidly made a major impact in our research towards improved prostate cancer metabolic imaging. Through his graduate studies in electrical engineering at Stanford University, Dr. Larson became an expert in creating basic electronic waveforms that are critical for optimal MRI. The new techniques he has implemented have improved the quality and reliability of prostate MR metabolic imaging. Through a collaboration with GE Healthcare, the largest MR scanner manufacturer in the US, these techniques are now in prototype testing for future clinical release so that these methods will be widespread radiological tools for prostate cancer imaging. Through this academic-industry partnership funded by a grant from the US National Institutes of Health (NIH), new imaging methods are now being refined and distributed to other prostate cancer imaging sites. These collaborations have been extremely fruitful and include Dr. Hricak’s group at the Memorial Sloan-Kettering Cancer Center in New York which is also supported by the Sir Peter and Lady Michael Foundation. The fostering of these collaborations is a key component in developing and applying new methods for improved prostate cancer care. The goal of this collaborative work is to have the new imaging techniques developed at UCSF to be soon available at hundreds of sites around the world for improved prostate cancer delineation and characterization before and after therapy.

Also, Dr. Larson and other members of Dr. Vigneron’s group are working on an exciting new metabolic imaging technique with General Electric Healthcare that will take somewhat longer to develop but provides over 50,000-fold improvement for imaging cellular metabolism. This new method, called hyperpolarized carbon-13 imaging, was developed by GE scientists and through a collaboration with UCSF, this method is being improved with the goal of initiating the first prostate cancer patient trial next year. Initial studies in prostate cancer cell cultures and model systems have shown the ability to detect the abnormal metabolism of prostate cancer and differences with progression and response to therapy. This extraordinary new technique has the potential to become an important new radiological tool for metabolic imaging by directly observing specific metabolic pathways in prostate cancer that can characterize tumor aggressiveness and therapy response.

Memorial Sloan-Kettering Cancer Center

Funding from the Pelican Foundation is allowing researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) to explore exciting new approaches for imaging prostate cancer at the molecular level. Working under the guidance of Hedvig Hricak, MD, PhD, Pelican Fellow Jan Grimm, MD, PhD, is developing molecular imaging techniques that target prostate-specific membrane antigen (PSMA), an antigen highly expressed in prostate cancer cells and neovasculature. PSMA was originally cloned at MSKCC, and there is a long history of research on this transmembrane protein. Its expression correlates with the grade and prognosis of prostate cancer. Interestingly, it has also been found on the tumor vasculature of many other solid tumors and may therefore prove to be a useful target for imaging a wide variety of cancers. PSMA imaging promises to provide insights into prostate cancer biology. Furthermore, if translated to the clinic, it may allow improved prostate cancer detection and characterization, the development of new targeted therapies, and more precise monitoring of treatment effects.

Dr. Grimm is currently testing and exploring a novel magnetofluorescent nanoparticle that binds to PSMA and can be detected with MRI and optical imaging alike. This agent was developed over the last year and is now undergoing optimization. Several in vitro and in vivo imaging studies have shown its specific binding. Upcoming experiments will use this particle to monitor novel therapeutic approaches for prostate cancer.

Dr. Grimm is also exploring a novel optical imaging agent to detect prostate cancer through function of PSMA. This agent is being developed in collaboration with the expertise and capabilities of the organic chemistry core facility at MSKCC and is being studied extensively in vitro and also explored for patenting. It could have considerable potential for in vivo studies and may become a candidate for clinical application.

A portion of Dr. Grimm’s work on PSMA imaging was presented as an abstract at the World Molecular Imaging meeting in Nice, France in September 2008. Drs. Grimm and Hricak are deeply grateful for the Pelican Foundation’s continued support.

2007 Results

In 2007, the Sir Peter and Lady Michael Foundation underwrote three Pelican Fellows conducting postdoctoral prostate cancer imaging research at three leading medical institutions.

University of California San Francisco / Mission Bay

The continued support by the Sir Peter and Lady Michael Foundation over the past year has greatly benefited prostate cancer imaging research at UCSF. Under the direction of Professor Daniel Vigneron, Ph.D., the research focuses on developing improved methods for anatomic and metabolic imaging of prostate cancer. Such improved imaging is critical for guiding and evaluating emerging therapies, in the consensus view of participants of the Colloquium on Prostate Cancer, sponsored by the Pelican Cancer Foundation last year. This continues to be an under-funded area of research, but a very necessary one that offers great potential benefit to prostate cancer patients.

Over the past year, the funding from the Sir Peter and Lady Michael Foundation has supported the Pelican Fellow, Dr. Albert Chen’s research developing new prostate cancer imaging methods for diagnosing as well as guiding and monitoring treatment. His work has resulted in new magnetic resonance (MR) techniques which double the spatial resolution of MR anatomic and metabolic imaging and reduce the time as compared to currently commercially available techniques. Dr. Chen’s work has resulted in a recent publication in the Journal of Magnetic Resonance Imaging titled “High Speed 3T MR Spectroscopic Imaging of Prostate with Flyback Echo Planar Encoding”. He also presented his work titled “High Resolution MRSI and DTI of Prostate Cancer” at the May meeting of the International Society of Magnetic Resonance in Medicine in Berlin Germany. The new techniques he has developed allow more accurate determinations of the precise volume, shape and location of individual prostate cancers.

Based on this work, Dr. Vigneron’s group recently received a grant from the National Institutes of Health, to translate these basic methods into widespread clinical tools available world-wide. Through academic and industry partnerships, these methods are now being refined and distributed to other prostate cancer imaging sites. These collaborations have been extremely fruitful and include Dr. Hricak’s group at the Memorial Sloan-Kettering Cancer Center in New York which is also supported by the Sir Peter and Lady Michael Foundation. The fostering of these collaborations is a key component in developing and applying new methods for improved prostate cancer care. The goal of this collaborative work is to have the new imaging techniques developed at UCSF over the past few years to soon be available at hundreds of sites around the world for improved prostate cancer delineation and characterization before and after therapy.

Also, Drs. Vigneron and Chen are working on an exciting new metabolic imaging technique with General Electric Healthcare that will take somewhat longer to develop but offers over 50,000-fold improvement for imaging cellular metabolism. This new method, called hyperpolarized carbon-13 imaging, was developed by GE scientists and through collaboration with UCSF; this method is being improved with the goal of starting the first prostate cancer patient studies next year. Initial studies in prostate cancer cell cultures and model systems have shown the ability to detect the abnormal metabolism of prostate cancer and differences with progression and response to therapy. This is an extraordinary new technique that has the potential to become an important new radiological tool for metabolic imaging by directly observing key cellular bioenergetic processes involved in cancer development and therapy response.

Memorial Sloan-Kettering Cancer Center

Dr. Jan Grimm is entering his second year as a Pelican fellow. His primary focus is molecular imaging of prostate cancer. Dr. Grimm received his medical degree from the University of Hamburg, Germany and his PhD from the University of Kiel, Germany. His postdoctoral training in Molecular Imaging was at Harvard Medical School, Massachusetts. After his postdoctoral training he was appointed as a faculty member at Harvard Medical School. In 2006 he joined Memorial Sloan-Kettering Cancer Center to introduce molecular imaging with nanoparticles for MRI and optical imaging. In order to facilitate translational molecular imaging research he will have an additional focus on preclinical and clinical nuclear medicine.

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and neovasculature (the blood vessels that feed the tumor). The level of PSMA expression in prostate cancer correlates with the aggressiveness of the disease. Dr. Grimm’s research is aimed at developing novel imaging agents to detect PSMA and study its biology.

Peptides were synthesized that bind to PSMA. In vitro studies showed that the binding of the peptides was greater on PSMA expressing cells and increased with increasing peptide concentration. To construct a probe suitable for both magnetic resonance and optical imaging, the peptides were bound to iron oxide particles carrying fluorescent molecules. Pilot in-vivo animal imaging studies showed binding of the constructed probe to PSMA-expressing tumor and not to control tumor. These results suggest that the probe could be used to detect and study the function of PSMA in prostate cancer in animals. Ultimately, it may be possible to transfer the new imaging probe to the clinical arena to detect and characterize prostate cancer in humans and to monitor novel therapeutic approaches, such as adoptive immunotherapy.

The Pelican Cancer Foundation

I want to thank the Trustees of the Pelican Cancer Foundation for their support during my last two years in conducting the focal therapy research program in prostate cancer, under the supervision of Mark Emberton.

The research is world-class and we should all be excited by the fellowship supporting work that can produce tangible benefits for men with prostate cancer within 2-5 years. At present, far too many men are encouraged and advised to have radical surgery or radiotherapy which can be extremely detrimental to their quality of life. This work, by targeting only the tumour and not the whole gland will hopefully provide the quality of life after treatment that men want. Such truly translational work is rare to find and I am honoured to have been a part of it.

I have presented at numerous national and international conferences and published widely and have been at pains to emphasise the support offered by Pelican Cancer Foundation. This has raised the profile of PCF and will hopefully bear fruits in the near future. In addition, such conferences have allowed me to debate and engage an international audience of some of the greatest scientific minds in cancer of the urinary tract.

2006 Results

University of California San Francisco
California Institute for Quantitative Biomedical Research

Prostate cancer imaging research at UCSF has benefited greatly from the support provided in February 2006 by the Sir Peter and Lady Michael Foundation. Under the direction of Daniel Vigneron, Ph.D., the research focuses on improving the anatomic and metabolic imaging of prostate cancer. Such improved imaging is critical for guiding and evaluating emerging therapies, in the consensus view of participants of the Colloquium on Prostate Cancer, sponsored by the Pelican Cancer Foundation in late March 2006. This is an under-funded area of research, but a very necessary one that offers great potential benefit to prostate cancer patients.

Our group has made substantial progress toward improved imaging methods for diagnosing as well as guiding and monitoring treatment. We have developed new magnetic resonance (MR) techniques to double the spatial resolution of MR anatomic and metabolic imaging over currently commercially available techniques. This improvement in spatial resolution allows more accurate determinations of the precise volume, shape and location of individual prostate cancers. A key member of the research team is the Pelican Fellow, Albert Chen, Ph.D. He presented the project and the methods developed through it at the May meeting of the International Society of Magnetic Resonance in Medicine, and the report has been published as follows: Chen AP, Oh J, Han E, Xu D, Kurhanewicz J, Vigneron D. Multi-Parametric MR Imaging of Prostate Cancer at 3T. ISMRM Fourteenth Scientific Meeting, Seattle, Washington, May 2006, p 360.

Dr. Chen has also worked on a novel MR acquisition technique for much faster metabolic MR imaging with up to 8-fold increase in speed and spatial coverage as compared to prior techniques. This work has been accepted for publication in the Journal of Magnetic Resonance Imaging as follows: Chen AP, Cunningham CH, Ozturk E, Xu D, Hurd RE, Kelley DAC, Pauly JM, Kurhanewicz J, Nelson SJ, Vigneron DB. High Speed 3T MR Spectroscopic Imaging of Prostate with Flyback Echo Planar Encoding. JMRI .

Fruitful collaborations have also been established as a result of the Foundation’s support. My participation at the Pelican Prostate Cancer Colloquium in Basingstoke increased my awareness of recent developments in therapy and imaging by research groups in Europe and the US, and fostered multi-site communication and collaboration. For example, we are now collaborating with Dr. Lowry’s research group in Hull, who are utilizing the new 3T prostate MR metabolic imaging sequence we developed at UCSF in their own research projects.

I am gratified that we have achieved significant progress within the budget established for this project. During the remainder of the grant period, we will continue to further improve and refine MR techniques to better define the presence, location and extent of individual prostate cancers. Future projects will validate these methods in patient trials prior to and following therapy.

Dr. Dan Vigneron

Memorial Sloan-Kettering Cancer Center

Dr. Hedvig Hricak, the leader of the prostate imaging research group at MSKCC, is pleased to announce that Dr. Jan Grimm has been selected as a 2007 Pelican Fellow. Dr. Grimm, a radiologist by training, recently joined the radiology department at MSKCC after spending more than four years in molecular imaging research, first as a fellow and later as a faculty member at the Harvard Medical School. At MSKCC he will gain expertise in clinical prostate imaging and will carry out research to develop molecular imaging approaches for prostate cancer. As the foremost suitable target he has chosen PSMA, an antigen highly expressed in prostate cancer cells and neovasculature. Dr. Grimm is seeking to develop novel imaging agents to detect the PSMA antigen itself and its enzymatic function, utilizing different types of ligands. Various labels for optical, nuclear, ultrasound and MR imaging are being explored in order to find the most effective and applicable combination of ligand and imaging modality. The experimental approach allows for simple combination of ligands with various labels and includes multimodality imaging (e.g., combining optical imaging with MRI). For some aspects of the research, the expertise and capabilities of the organic chemistry core facility at MSKCC are being utilized. Once an optimal imaging agent is described it will be used to study the function of PSMA in prostate cancer and also to monitor novel therapeutic approaches such as adoptive immunotherapy. In collaboration with other laboratories at MSKCC a transgenic mouse will be developed that expresses human PSMA; this will help to transfer the imaging agent into the clinical arena, which is the ultimate goal of the research study. Initial results show binding of some of the chosen ligands to prostate cancer cells in vivo.

The Pelican Cancer Foundation Prostate Colloquium
27th March – 28th March 2006

Prostate cancer management is fraught with difficulties. The decision a man with localized prostate cancer faces lies between such extremes of care, active surveillance and radical treatment, that the ultimate outcome of this process can have tremendous implications on his psychological and physical wellbeing. The difficulties, however, commence not at the time of the man being told that he has prostate cancer, but when he or his physician decide to carry out a simple blood test, PSA, in order to screen for the possibility of prostate cancer. This test is non-specific and much recent evidence points to no ‘safe’ value below which a man can be reassured that he has no cancer. If he then chooses, rightly or wrongly, to have a prostate biopsy on the basis of that blood test the biopsy technique itself has limited accuracy in detection of cancer. Firstly, it can miss significant cancer because of sampling error. Secondly, its detection of cancer is indiscriminate for it has no way of differentiating between insignificant cancer (which over 50% of 50 year olds have and will die with rather than from) and significant cancer (which is likely to impact on a man’s life expectancy).

This symposium was convened by Sir Peter Michael who saw medical research dominated by much in the field of molecular genetics and pharmacology – all well-deserving areas – at the expense of a lack of clinical and technological research. Our aim is to encourage activity in areas which are equally important but at times neglected in order to redress this balance. The Inaugural Pelican Cancer Foundation Prostate Colloquium was convened to bring together a small group of international researchers with the specific aims of encouraging debate and collaboration into the minimally invasive diagnosis and treatment of prostate cancer, for the betterment of the scores of men that are increasingly concerned or afflicted with this condition.

Mark Emberton, MD, FRCS(Urol),
FRCS Reader in Interventional Oncology
The Institute of Urology and Nephrology
University College London, United Kingdom.