By 2005, AdMeTech Foundation’s Brain Trust meetings emerged as one of the most important directions of AdMeTech’s research program. The 2005-2007 Brain Trust meetings and Public Conferences made a profound impact on research and education in the area of prostate imaging and image-guided treatment.

AdMeTech Foundation held multi-disciplinary, multi-institutional Brain Trust meetings in February 2004, October 2005, March 2006 and a series of meetings in early 2007. These meetings evaluated and determined the emerging research priorities, developed novel research ideas and selected high-impact projects.  Participants in those meetings included not only leading researchers, but also representatives of all major private and public funding entities, including Michael Milken’s Prostate Cancer Foundation, Department of Defense, National Institute of Biomedical Imaging and Bioengineering, National Cancer Institute and industry to ensure that:

1) AdMeTech Foundation’s selection of the unique research that's not funded by other organizations;  
2) The continuity of the selected research projects; and
3) Coordination of the AdMeTech’s efforts with other major funding entities and related strategic decisions.

The research conducted between 2005 and 2008 was the direct result of the Brain Trust meetings of February 2004, October 2005, March 2006, and early 2007 and continued to result in the development of novel, breakthrough imaging methods for early detection, accurate diagnosis, and minimally-invasive treatment of prostate cancer.  These imaging methods are based largely on the in vivo visualization of novel molecular markers which have been shown by in vitro experiments to be specific to prostate cancer. Each team identified a novel imaging agent that made it possible to target prostate cancer-specific molecules. The specific major goals accomplished by each subcontract are summarized below:

1) Dr. Martin Pomper (Johns Hopkins University)

Key Accomplishment:
Developed a series of novel, prostate specific membrane antigen (PSMA)-targeting molecular imaging agents, and the preliminary results are so promising that they warranted human imaging.  The potential of this work was recognized with grants from the prestigious Patrick Walsh Foundation and the National Institute of Health, which provided further funding for its continuation. While Dr. Pomper started with PET imaging, he is currently testing these agents for optical imaging.

Timeline of Accomplishment:
Within one year after funding

Impact on the attraction of talented investigators into prostate imaging:
Dr. Pomper, one of the leaders of molecular imaging, has not been involved with prostate imaging until he participated in the AdMeTech Foundation’s Brain Trust meeting of August 2001. Since that time, prostate imaging has become the major focus of this research.

2) Dr. Angelo DeMarzo (Johns Hopkins University)

Key Accomplishment:
Dr. DeMarzo’s team successfully identified molecular markers for the AMACR gene, and demonstrated their specificity to prostate cancer, as opposed to benign tissue. In addition, Dr. DeMarzo created a vector system for the delivery of imaging agents for the visualization the AMACR gene in vivo. Sufficient sensitivity of this novel imaging method to detect prostate cancer was achieved in animal models.  The exciting promise of this research was recognized by an award from the National Medical Association at its 2005 Annual Meeting.

Timeline of Accomplishment:
Within one year after funding

Impact on the attraction of talented investigators into prostate imaging:
Dr. DeMarzo is one of the pioneers of molecular pathology of prostate cancer who was not involved in prostate imaging until he participated in our Brain Trust meetings and public conferences starting in 1999.

3) Dr. Kimberly Kelly and Dr. Ralph Weissleder (Massachusetts General Hospital)

Key Accomplishment:
Dr. Kelly’s team pioneered an imaging method that targeted the visualization of the molecular marker Hepsin. Dr. Kelly discovered that the Hepsin-specific peptide was able to bind selectively to prostate cancer.The results indicate a breakthrough potential of this imaging agent using optical imaging: The Hepsin-specific peptide was able to diagnose prostate cancer with a specificity of 100%, a false positive rate of 0%, and a false negative rate of 0%. This research was published in Cancer Research.

Timeline of Accomplishment:
Within one year after funding

Impact on the attraction of talented investigators into prostate imaging:
Dr. Kelly is a member of the world-leading molecular imaging team of Dr. Ralph Weissleder, and this funding made it possible for her to focus on this exciting project in prostate imaging.

4) Dr. Mark Rosen (University of Pennsylvania)

Key Goal:
To identify whether ultra-high resolution, experimental high-field MRI improves localization and staging of prostate cancer.

Key Accomplishments:

1)Successful design and phantom testing of high-field (4T) dual-loop endorectal coil prototypes;
2) Successful design and in vivo use of the dual loop balloon endorectal coil at 3T; and
3) Performance evaluation of 3T dual loop coil relative to standard commercial 1.5T.
These results are extremely encouraging, and suggest that the dual loop endorectal coil design is a viable means of improving image quality in high-precision, high-field prostate MRI.

5) Dr. Ulrich von Andrian (Harvard Medical School)

Key Goals:
To apply a single-cell, unique intravital microscopy technique for studies of basic biology of prostate cancer metastases and their response to treatment to:

1) Explore the molecular and cellular mechanisms of prostate cancer cell dissemination, particularly in the bone  tissue; and
2) Visualize interactions of prostate cancer cells with bone and bone marrow in tumor-bearing mice.

1) Developed fluorescent dye for prostate cancer cell labeling;
2) Discovered that prostate cancer cells possess low bone marrow tropism in short-term homing experiments; and
3) Demonstrated that prostate cancer cells have a clear capacity to home to peripheral lymph nodes.

Impact on the attraction of talented investigators into prostate imaging:
Dr. Van Adrian did not consider to apply his unique optical technology to prostate cancer imaging until he and his team participated in the AdMeTech’s Brain Trust meetings in 2006.

6) Dr. Nathan McDannold and Dr. Clare Tempany (Brigham & Women’s Hospital, Harvard Medical School)

Key Goals:
To test whether image-guided, minimally-invasive thermal ablation methods for the treatment of prostate cancer, such as focus ultrasound, can be improved by applying functional MRI techniques to assess tissue perfusion, oxygenation, and temperature before and after treatment.  These studies will have the potential to substantially improve thermal cancer therapies through optimization of treatment planning and monitoring.

Key Accomplishments:

1) Development and pilot testing of software to estimate perfusion based on dynamic contrast enhanced imaging, which was used to estimate prostate cooling by the focus ultrasound treatment device; and
2) Implementation of motion tracking algorithms to handle prostate motion, which is one of the fundamental challenges in prostate imaging.